CN114470116A

CN114470116A - Traditional Chinese medicine composition for influencing expression level of gastric mucosa oncogene

Info

Publication number: CN114470116A
Application number: CN202210335520.2A
Authority: CN
Inventors: 陆敏; 樊欣钰
Original assignee: Nanjing City Lishui District Chinese Medicine Hospital
Current assignee: Nanjing City Lishui District Chinese Medicine Hospital
Priority date: 2022-03-24
Filing date: 2022-03-24
Publication date: 2022-05-13
Anticipated expiration: 2042-03-24
Also published as: CN114470116B

Abstract

The invention belongs to the application field of traditional Chinese medicines in treating diseases caused by the influence of the expression levels of oncogene mutant p53 and oncogene MDM2 on the gastric mucosa of a patient, and particularly relates to the specific application in treating diseases caused by the mechanism, such as chronic atrophic gastritis. The technical scheme is that the traditional Chinese medicine composition for influencing the expression level of the gastric mucosa oncogene comprises the following components in parts by weight: 3000 portions of astragalus 400-. Immunohistochemical analysis shows that the expression of oncogene mutant p53 and MDM2 is inhibited to be related, so that the medicine has better curative effect on patients with chronic atrophic gastritis, and particularly has better curative effect on the aspects of improving gastral cavity fullness or dull pain, stomach pressing or warming preference, loose stool, fatigue and weakness, short breath and no speaking and the like compared with a gold standard medicine, namely morrhodin; and can effectively improve pathological states of gastric mucosa atrophy, intestinal metaplasia, chronic inflammation, activity and the like and delay the atrophy process.

Description

Traditional Chinese medicine composition for influencing expression level of gastric mucosa oncogene

Technical Field

The invention belongs to the application field of traditional Chinese medicines in treating diseases caused by the influence of the expression levels of oncogene mutant p53 and oncogene MDM2 on the gastric mucosa of a patient, and particularly relates to the specific application in the diseases caused by the mechanism, such as chronic atrophic gastritis (spleen and stomach weakness syndrome).

Background

In the 'research progress of correlation between p53 and gastrointestinal malignant tumors' of the university of Geqian et al, J.Med.Med.Med.Med.Med.Progestis 2016, 10 th year, it was pointed out that p53 can be divided into a wild tumor suppressor genotype (wt-p53) and a mutant tumor suppressor genotype (mt-p 53). Oncogene mutant p53 and MDM2 are related to cell proliferation and apoptosis, and the protein expression level of the oncogene mutant p53 and MDM2 is important related to the occurrence and development of chronic atrophic gastritis (hereinafter, CAG) and can directly or indirectly mediate various downstream reactions and also directly cause imbalance of cell proliferation and apoptosis, activation of cancer/cancer suppressor genes and abnormity of signal transduction pathways. Wherein chronic atrophic gastritis is a common chronic disease in the digestive tract caused by abnormal expression level of the gene. The chronic atrophic gastritis is clinically classified according to the pathological characteristics of the chronic gastritis, the main clinical manifestations of the chronic atrophic gastritis are generally known as gastritis, the chronic atrophic gastritis is mainly nonspecific manifestations such as fullness in the abdomen, epigastric pain and belching, and the chronic atrophic gastritis is named as the precancerous state of the stomach because the chronic atrophic gastritis has a certain carcinogenic rate and is located at the initial part of the Correa cascade reaction in the classic mode of intestinal gastric cancer. Meanwhile, as a chronic digestive tract disease accompanied for a long time, patients are often in an overstrained mood, even the symptoms are aggravated, and the mental and economic stresses are caused to the patients. In recent years, the prevalence rate of CAG tends to increase, which may be related to factors such as increased living cost of people, poor dietary preference, irregular work and rest time, and increased attention on self health after economic level is improved.

At present, western medicine treatment mainly aims at eradicating HP and treating symptoms, and no special targeted treatment scheme is available.

Disclosure of Invention

Object of the Invention

A Chinese medicinal composition is searched in the Chinese medical treasury to treat diseases such as chronic atrophic gastritis by inhibiting the expression level of gastric mucosa oncogene mutant p53 and MDM 2.

Adopts the technical proposal

A traditional Chinese medicine composition capable of influencing the expression level of gastric mucosa oncogenes comprises the following components in parts by weight: 3000 portions of astragalus 400-.

Further, the mixture ratio is 600-2500 parts of astragalus root, 600-1200 parts of ganoderma lucidum, 700-3000 parts of coix seed, 600-1200 parts of dried orange peel, 700-3000 parts of Chinese sage herb and 700-3000 parts of spreading hedyotis herb.

Furthermore, the mixture ratio is 1000-1300 parts of astragalus root, 900 parts of ganoderma lucidum, 1200-1800 parts of coix seed, 900 parts of dried orange peel, 1200-1800 parts of Chinese sage herb and 1200-1800 parts of oldenlandia diffusa.

Advantageous effects

Immunohistochemical analysis shows that the inhibition of the expression correlation of gastric mucosa oncogene mutant p53 and MDM2 has better curative effect on patients with chronic atrophic gastritis (spleen and stomach weakness syndrome), and particularly has better curative effect on the aspects of improving gastric cavity fullness or dull pain, stomach pressing or warming preference, loose stool, fatigue and weakness, short breath and no desire to speak and the like compared with the gold standard medicament- -Moluo Hua Luo; and can effectively improve pathological states of gastric mucosa atrophy, intestinal metaplasia, chronic inflammation, activity and the like and delay the atrophy process.

In the formula of the traditional Chinese medicine composition, astragalus root is sweet and warm and is a monarch drug, and is an essential drug for tonifying qi, and tonifying middle-jiao and yang qi are lifted; the lucid ganoderma is used as a minister, supplements qi, calms the nerves and calms the heart and the kidney, is complementary with monarch drugs and takes the innate and acquired root into consideration; the herba Hedyotidis Diffusae is slightly bitter, sweet and cold, and the herba Salviae chinensis is pungent and cold, and is used as adjuvant drug. Coix seed, semen Coicis, sweet and bland in taste, induces diuresis and excrets dampness, and also can invigorate spleen; the tangerine peel is pungent and warm in property, regulates qi, relieves epigastric distention, eliminates dampness and phlegm, the upper 2 flavors enter lung and spleen channels, and the tangerine peel is used as a guiding drug, so that the tangerine peel can not only promote qi stagnation, invigorate spleen and dissipate stagnation, but also lead phlegm-dampness to a certain extent; the medicines are combined to play the effects of invigorating spleen and tonifying middle-jiao, eliminating dampness and dissipating stagnation.

Drawings

FIG. 1 expression profile of p53 before treatment in the study group.

FIG. 2 expression profile of p53 after treatment in the study group.

FIG. 3 expression profile of p53 before treatment in control group.

FIG. 4 expression profile of p53 after control treatment.

Figure 5 expression profile of MDM2 before treatment in the study group.

Figure 6 expression profile of MDM2 after treatment in the study group.

Figure 7 expression profile of MDM2 before treatment of the control group.

Figure 8 expression profile of MDM2 after control treatment.

Detailed Description

In the examples listed in the specification, the specific mixture ratio of 12g of astragalus root, 8g of ganoderma lucidum, 15g of coix seed, 8g of dried orange peel, 15g of Chinese sage herb and 15g of spreading hedyotis herb is adopted.

1 content and method of implementation of the study

1.1 case Source and grouping

The study cases of the subject are derived from 68 CAG (spleen and stomach weakness syndrome) patients in the department of gastroenterology of the combined Chinese and western medicine Hospital in Jiangsu province, and are randomly grouped into 34 cases each.

Moluodan is used as a contrast medicine, the effective rate mu l of the traditional Chinese medicine composition is estimated to be 90 percent according to early clinical observation, the effective rate mu 2 of the Moluodan serving as the contrast is reported to be 60 percent in literature,

the two-sided test α is set to 0.05, β to 0.2, Z_α＝1.96，Z_βThe amount of samples per group was calculated according to the statistical formula at 0.84:

considering that the treatment period and gastroscope review period in the study are longer, the visit rate is set as 15%, and N ═ N × (1+ 20%) is approximately equal to 34, so 34 patients are respectively collected in the study group and the control group, and 68 patients are totally collected.

1.2 case selection

1.2.1 diagnostic criteria

Western medicine: by adopting the consensus opinion on Chinese chronic gastritis of the Chinese medical society of 2017, CAG (computer aided manufacturing), namely visible mucous membrane red and white under an endoscope, mainly takes white phase as main part, folds become flat and even disappear, and partial mucous membrane blood vessels appear; can be accompanied by the manifestations of mucosal particles or nodular shapes, etc.; there are 5 histopathological changes, including Hp, motility, inflammatory response, atrophy and intestinal metaplasia. Since this study discusses the Hp negative CAG patients, it will be discussed from the latter four.

Traditional Chinese medicine: according to the diagnosis standard of ' weakness of spleen and stomach ' of the cooperation opinion of Chinese and Western medicine combined diagnosis and treatment for chronic atrophic gastritis ' of 2017 edition, the main symptoms are as follows: firstly, gastric cavity fullness or dull pain; ② the stomach is good for pressing or warm. The secondary symptoms are as follows: firstly, eating less and eating poor; ② loose stool; third, lassitude and hypodynamia; fourthly, shortness of breath and no speaking desire; fifthly, the stomach is stuffy after eating. Tongue pulse: pale tongue and thready and weak pulse. The syndrome type is determined: the main symptoms and tongue symptoms are essential, and more than 2 items of secondary symptoms are added, referring to pulse conditions.

1.2.2 case inclusion criteria

The age is between 20 and 80 years, and the nature is not limited;

the western medicine diagnosis meets the CAG diagnosis standard;

thirdly, the traditional Chinese medicine distinguishes the syndrome to belong to the weak spleen and stomach;

the treatment is carried out voluntarily, and the clinical compliance is better;

the Hp detection is negative.

1.2.3 case exclusion criteria

The pathological diagnosis shows that the patient is indeed cancerated;

② patients with serious primary diseases, such as heart, brain, liver, kidney, blood system or mental diseases;

③ for the treatment of drug allergy;

fourthly, pregnant women or breast feeding patients;

difficulty in describing clinical symptoms or failure to collaborate;

sixthly, the Hp detection is positive.

1.2.4 Observation termination criteria

The patient stops taking the medicine due to serious allergy or adverse reaction;

② patients with other serious diseases during the period of illness deterioration or medicine taking;

case data serious deletion such as failure to make a repeat visit or complete examination on time;

fourthly, the patient requires withdrawal by the patient.

1.3 treatment regimens

The traditional Chinese medicine composition comprises the following components: 12g of astragalus, 8g of lucid ganoderma, 15g of coix seeds, 8g of dried orange peel, 15g of Chinese sage herb and 15g of spreading hedyotis herb, which are decocted by a decoction chamber in a unified way.

Specification of Moluodan: 16 pills (1.84g/16 pills) 18 bags, handan pharmaceutical products company, approved document: the national standard of medicine Z20090013.

Study group: the traditional Chinese medicine composition is decocted, one dose is taken every day in the morning and evening.

Control group: moluodan, 1.84 g/time, 3 times/day.

The treatment course is 12 weeks.

1.4 Observation index

1.4.1 general case

The patients were observed for general condition and the differences between the two groups were compared, as detailed in the study results section.

1.4.2 immunohistochemical method for detecting contents of mutant p53 and MDM2 in gastric mucosa

Randomly selecting gastric mucosa tissue sections of 7 patients in a control group and a research group for immunohistochemical detection, taking 1-2 corresponding gastric mucosa tissue specimens before and after treatment of each person, and moving 3-4 continuous coronal sections with the thickness of 2 microns on a microtome. The operation steps are as follows: slicing xylene, dewaxing, and dewatering with alcohol step by step; the slices are placed in a citric acid buffer solution, heated for 20min by low fire in a microwave oven to restore the antigen, naturally cooled and washed by PBS for 5min multiplied by 3 times. Blocking with 3% peroxidase for 25min, washing with PBS for 5min × 3 times. 3% BSA was added dropwise to cover the tissue, and goat-derived rabbit serum primary antibody was added for blocking, and the mixture was refrigerated overnight at 4 ℃. Adding secondary antibody, washing with PBS for 5min × 3 times; labeling secondary antibody, and incubating for 50min at room temperature; washing with PBS for 5min × 3 times, dripping freshly prepared color developing agent, re-dyeing with hematoxylin for 3min, washing with running water, and removing blue; dewatering with alcohol step by step, and sealing.

Under a microscope with 200 times, images are collected through 5 discontinuous fields, and the Mean Optical Density (MOD) is measured and calculated by using software imagej, wherein the MOD is IOD/Area, and the expression levels of the proteins mt-p53 and MDM2 of the gastric mucosa are analyzed.

1.4.3 evaluation of curative Effect on clinical symptoms

The clinical curative effect of the subject is formulated according to the guiding principle of clinical research of new traditional Chinese medicines, the clinical manifestations of the gastric asthenia syndrome of the Chinese traditional and western medicine integrated society of 2017, the consensus opinion of the Chinese traditional and western medicine integrated diagnosis and treatment of chronic atrophic gastritis, the tongue pulse and the spleen and stomach weakness syndrome clinical manifestations of the CAG are comprehensively evaluated, and the clinical curative effect is judged by comparing 1 time of record before and after treatment according to corresponding scores of the major symptoms and the minor symptoms. Each single Chinese medicine syndrome is divided into 4 grades of none, light, medium and heavy, and assigned respectively.

② evaluation standard of curative effect:

the clinical cure is as follows: the syndrome basically disappears, and the integral is reduced to more than or equal to 95 percent. The effect is shown: the syndrome volume is reduced by more than or equal to 70 percent compared with that before treatment. The method has the following advantages: the syndrome volume is reduced by more than or equal to 30 percent compared with that before treatment. And (4) invalidation: the syndrome volume was reduced by < 30% compared to pre-treatment.

The efficacy score (nimodipine method) — [ (pre-treatment-post-treatment integral) ÷ pre-treatment syndrome total integral ] × 100%.

1.4.4 gastroscope and pathological evaluation

The gastroscope was operated by 2 fixed experienced physicians, the gastric mucosal state was observed under the gastroscope, and the pathologically obtained sites before and after treatment were fixed, and tissue biopsy could be taken separately if there was a suspicious lesion. HE staining was performed on biopsy tissues before and after treatment. According to the suggestions of Chinese medical society of gastroenterology division of China's consensus on chronic gastritis in clinic and 2017, CAG patients review the gastroscope pathology after 1 year, evaluate the indexes of atrophy, intestinal metaplasia, chronic inflammation, activity and the like, and compare the curative effects before and after treatment.

The clinical cure is as follows: the chronic inflammation of the mucous membrane is obviously better transferred to mild degree by the repeated examination of the gastroscope, and the gland atrophy, the intestinal metaplasia and the intraepithelial neoplasia are verified to be recovered to be normal or disappeared by the examination of the histopathology.

The effect is shown: the chronic inflammation of the mucous membrane is checked to be improved by gastroscope, and the gland atrophy, the intestinal metaplasia and the intraepithelial neoplasia are confirmed to be recovered to be normal or reduced by 2 grades by histopathological examination.

The method has the following advantages: the lesion range of the mucous membrane is narrowed by 1/2 in gastroscope review, and the chronic inflammation is reduced by more than 1 grade degree as proved by the pathological histological examination, and the gland atrophy, the intestinal metaplasia and the intraepithelial neoplasia are reduced.

And (4) invalidation: failing to meet the above criteria or deteriorating instead.

1.5 statistical methods

Analysis was performed using SPSS 25.0. Metering data adoption

It is shown that for those who fit a normal distributor, the t-test is applied, and for those who do not fit a normal distributor, the rank-sum test is applied. The difference between groups is compared by chi-square test, and the difference is statistically significant when P is less than 0.05.

2 results of the study

68 CAG patients are randomly grouped, and each group has 34 patients, 3 patients in a research group and 2 patients in a control group do not have gastroscopy in the treatment process because the treatment period and the review time are longer. Therefore, the study group and the control group, which were finally included in the analysis of the results, were 31 and 32, respectively, and there was no significant adverse reaction among patients in each group during the treatment period.

2.1 general data comparison

The study group included 14 males and 17 females, the control group included 15 males and 17 females, and the chi-square test showed two groups of gender comparisons chi²1.0, 0.891 and 0.05 > P, without significant difference.

The analysis of t-test shows that the ages of the study groups are 31-79 years, the mean age is 53.94 years, the age of the control group is 36-79 years, the mean age is 59.38 years, the t is 1.958, and the P is 0.055 & gt 0.05, which has no obvious difference. The disease course of the study group is distributed between 1 and 22 years, the average disease course is 4.32 years, the disease course of the control group is distributed between 1 and 10 years, the average disease course is 4.06 years, t is 0.311, P is 0.757 and is more than 0.05, and no obvious difference exists. The patients in the study group and the control group have no obvious difference in age, sex and disease course and are comparable. See table 1 for details.

TABLE 1 comparison of patient general conditions

2.2 comparison of expression levels of oncogene mutant p53 and oncogene MDM2 before and after treatment

As shown in Table 2, there was no significant difference in MOD values between the two groups of mt-P53 and MDM2 before treatment (P > 0.05) according to the t-test analysis. After treatment, compared with the study group, MOD values of mt-P53 and MDM2 are reduced compared with the MOD values before treatment (the P is less than 0.05); the MOD values of the control group mt-P53 and MDM2 are obviously reduced (the P is less than 0.05); the MOD values of mt-P53 and MDM2 in research groups are obviously lower than those of a control group (P is less than 0.05), and the traditional Chinese medicine composition and morrhodin can inhibit protein level expression of mt-P53 and MDM2, wherein the traditional Chinese medicine composition has a better inhibition effect. See figures 1 to 8 of the drawings of the specification for details.

Fig. 1 is an expression map of p53 before treatment in the study group, fig. 2 is an expression map of p53 after treatment in the study group, fig. 3 is an expression map of p53 before treatment in the control group, fig. 4 is an expression map of p53 after treatment in the control group, fig. 5 is an expression map of MDM2 before treatment in the study group, fig. 6 is an expression map of MDM2 after treatment in the study group, fig. 7 is an expression map of MDM2 before treatment in the control group, and fig. 8 is an expression map of MDM2 after treatment in the control group.

TABLE 2 MOD-value comparison of two sets of mt-p53, MDM2

Note: t-test analysis indicated, # indicates inter-group comparison P < 0.05 and # indicates intra-group comparison P < 0.05.

The comparison between two groups is carried out, t is 0.784 and P is 0.436-0.05 in the comparison between mt-P53 before treatment; after treatment, the comparison between groups is t 2.191, and P0.032 < 0.05; in-group comparison, study group t is 3.832, P is 0.000 < 0.01, control group t is 2.396, and P is 0.019 < 0.05. MDM2 pre-treatment group comparison t 1.428, P0.158 > 0.05; post-treatment comparisons between groups t 2.154, P0.035 < 0.05; in-group comparison, study group t is 5.629, P is 0.000 < 0.01, control group t is 2.070, and P is 0.042 < 0.05.

2.3 comparison of Chinese medicine syndrome before and after treatment

2.3.1 comparison of clinical symptoms

The rank sum test analysis shows that the symptoms of the two groups are not obviously different before treatment (P is more than 0.05), and the two groups have comparability. After treatment, the group contrast suggests that the score of each symptom in the treatment group is reduced (P is less than 0.05) compared with that before treatment, except that the stomach is favored by pressing or warming, loose stool, short breath and no speaking (P is more than 0.05), the rest symptoms are improved (P is less than 0.05) compared with that before treatment; the comparison result between the two groups shows that the residual symptoms of the treatment group are reduced compared with the integral of the control group (P is less than 0.05) except that the food is poor and the epigastric distress is caused after eating (P is more than 0.05). See table 3 for details.

TABLE 3 two sets of symptom score comparisons

Note: rank-sum test, # indicates P < 0.05 between groups and # indicates P < 0.05 within groups.

Compared with the former two groups, the stomach is full of gastric cavity or dull pain P ═ 0.548, stomach is warm or happy, P ═ 0.271, loose stool P ═ 0.592, lassitude and hypodynamia P ═ 0.694, anorexia P ═ 0.641, short breath and disinclination to speak P ═ 0.421, and epigastric distress P ═ 0.563 after eating; after treatment, the stomach is contrasted with the epigastric fullness or dull pain P which is 0.011, the stomach is favored to press or warm P which is 0.035, the loose stool P which is 0.004, the lassitude and hypodynamia P which is 0.020, the appetite is poor and P which is 0.454, the short breath and disinclination to speak P which is 0.002 and the epigastric distress P which is 0.507. In the treatment group, the contrast of epigastric fullness or dull pain P is 0.000, stomach is favored by pressing or warm P is 0.001, loose stool P is 0.001, lassitude and hypodynamia P is 0.000, anorexia P is 0.001, short breath and no desire to speak P is 0.000, and epigastric distress P is 0.000 after eating; in the control group, the gastric cavity fullness or dull pain P is 0.000, the stomach is hot or warm with preference P0.478, loose stool with preference P0.190, lassitude with preference P0.012, anorexia with preference P0.000, short breath with preference P0.159, and gastric cavity oppression with preference P0.000 after eating.

2.3.2 clinical efficacy comparison

As shown in Table 4, after the treatment, the total effective rates of the treatment group and the control group are 87.10% and 62.50% respectively, and the difference between the two groups has statistical significance (chi)²＝5.028，P＝0.025＜0.05)。

TABLE 4 comparative efficacy of the two groups of TCM drugs (examples,%)

2.4 comparison of gastroscope pathological results before and after treatment

As shown in Table 5, after the treatment, the total effective rate of atrophy of the study group is 61.29%, the total effective rate of atrophy of the control group is 50.00%, and no significant difference (X) exists between the two groups according to chi-square test calculation²＝0.813，P＝0.367＞0.05)。

TABLE 5 comparison of the therapeutic effects of atrophy in two groups (example,%)

As shown in Table 6, after the treatment, the total effective rate of the intestinal digestion of the study group and the control group is 58.06% and 34.38% respectively, and no significant difference (chi-type) is generated by chi-square test calculation²＝3.557，P＝0.059＞0.05)。

TABLE 6 comparison of the effects of intestinal chemotherapy in two groups (example,%)

As shown in Table 7, after the treatment, the total effective rate of chronic inflammation was 48.39% and 3.13% respectively, and the difference was statistically significant (X)²＝17.026，P＝0.000＜0.01)。

Table 7 two comparative treatment groups (examples,%)

As shown in Table 8, the activity total effective rates of the study group and the control group after treatment were 29.03% and 9.38%, respectively, and the difference was statistically significant (χ)²＝3.946，P＝0.047＜0.05)。

Table 8 two groups of active efficacy comparisons (example,%)

Discussion of 3

3.1 cubic basis and prescription analysis of the Chinese medicinal composition of the present invention

In the traditional Chinese medicine composition, the astragalus root is sweet and warm and is a monarch drug, so that the astragalus root is a vital drug for tonifying qi, tonifying middle-jiao and lifting yang qi; the lucid ganoderma is used as a minister, supplements qi, calms the nerves and calms the heart and the kidney, is complementary with monarch drugs and takes the innate and acquired root into consideration; the herba Hedyotidis Diffusae is slightly bitter, sweet and cold, and the herba Salviae chinensis is pungent and cold, and is used as adjuvant drug. Coix seed, semen Coicis, sweet and bland in taste, induces diuresis and excrets dampness, and also can invigorate spleen; the tangerine peel is pungent and warm, regulates qi, relieves epigastric distention, eliminates dampness and phlegm, the upper 2 medicines enter lung and spleen channels, and the tangerine peel is used as a guiding drug, so that the effects of activating qi of stasis, strengthening spleen and resolving masses and promoting phlegm-dampness are achieved; the medicines are combined to play the effects of invigorating spleen and tonifying middle-jiao, eliminating dampness and dissipating stagnation.

CAG is formed by classification of modern pathology on the basis of chronic gastritis, and the traditional disease names of traditional Chinese medicine can be summarized into diseases such as stomach ache, stomach fullness, eructation and the like according to the symptoms of the main digestive system of the traditional Chinese medicine. After the ancient and modern times, the CAG is closely related to the spleen, liver and kidney. In the treatise on the etiology and pathogenesis, the zang-fu organs are closely related to the transportation and reception of the stomach and fu organs because the zang-fu organs all receive the food's qi in the stomach. The spleen and stomach are related to each other and are located close to each other, and the two are "connected with each other by the membrane" and function to promote the body fluid flow of the stomach ", so they are involved in treating the diseases of the spleen and stomach, and when qi movement is blocked or not arrested, the corresponding function of the zang-fu organs is disordered. The four saints of heart source think that the middle energizer is the mechanism of harmonizing water and fire and ascending and descending the axis of the jin mu, suggesting that qi diseases cause the viscera to ascend and descend and lose the function of qi, so the core pathogenesis of CAG is the qi deficiency of spleen and stomach, accompanied by the pathogenic factors of dampness and blood stasis.

As a proved prescription of the traditional Chinese medicine and western medicine combined hospital digestive department in Jiangsu province, the traditional Chinese medicine composition disclosed by the invention is developed into a series of clinical and experimental researches in famous and old traditional Chinese medicine inheritance studios all over the country. The prescription comprises astragalus root, ganoderma lucidum, coix seed, dried orange peel, Chinese sage herb, oldenlandia diffusa and the like. Wherein, the astragalus root is a monarch drug, is sweet and warm and can tonify the middle warmer and lift yang qi, and is an essential drug for tonifying qi; the lucid ganoderma is used as a minister, supplements qi, calms the nerves and calms the heart and the kidney, is complementary with monarch drugs and takes the innate and acquired root into consideration; the herba Hedyotidis Diffusae is slightly bitter, sweet and cold, and the herba Salviae chinensis is pungent and cold, and is used as adjuvant drug. Coix seed, semen Coicis, for eliminating dampness and strengthening the spleen, Tangerine Peel, for regulating qi and eliminating dampness, 2 herbs enter lung and spleen meridians, and together act as guiding drugs, and they can promote qi stagnation, strengthen spleen and dissipate nodulation, and make phlegm-dampness go out; the medicines are combined to play the effects of invigorating spleen and tonifying middle-jiao, eliminating dampness and dissipating stagnation.

Astragalus root: astragalus root is a qi-tonifying holy medicine, and according to the characteristics of thin and thick smell, the functional characteristics of the medicine are summarized as rising and lowering and yang within yang, which suggests that astragalus root can strengthen superficies, promote toxicity, induce diuresis, promote granulation, etc., and can coordinate to protect all internal organs, tonify qi, strengthen the body resistance. The efficacy of the Chenyun is detailed in terms of' the astragalus root enters the spleen and dominates the muscles, enters the lung and enters the fur; the effective components of astragalus root, including quercetin, kaempferol and the like, are analyzed through network pharmacology by using Wenwort and the like, wherein the effective components of astragalus root, including astragalus root, the Wenwort and the like, are used for assisting the middle-jiao qi … … entering the triple energizer and assisting the reading, and core overlapping genes related to CAG are obtained, such as AKT1, TP53, IL6 and the like. When the gastric mucosa is injured, the astragalus can regulate and control downstream reaction through a target gene, further regulate and control mucosal defense factors, improve hemodynamics and antioxidant stress response, enhance gastric mucosa defense, regulate the autoimmune function of a CAG patient, promote gastrointestinal motility, even prevent canceration and the like.

Ganoderma lucidum: shi Er, also called Shi Er, is produced in Yan rock and shaped like the Geer Er. Ganoderma lucidum is classified into six products (red ganoderma, green ganoderma, yellow ganoderma, white ganoderma, black ganoderma and purple ganoderma) with five elements and sweet and even flavor, and the compendium of materia medica is mainly used for benefiting color after long-term eating until the old, causing no hunger and little urine. Improving eyesight and replenishing vital essence. Pharmacological research suggests that ganoderma has important effects on resisting tumor besides the functions of resisting inflammation and bacteria, protecting liver and kidney, regulating endocrine and the like. The ganoderma lucidum polysaccharide can be used as one of the main components, can inhibit tumor proliferation in multiple ways by regulating the expression of immune factors and tumor-related cells, has the characteristic of reversing the multidrug resistance of tumors, and improves partial drug concentration, thereby playing a role in inhibiting cancers. The ganoderma lucidum triterpenes can directly act on tumor cells to generate certain biological toxicity, so that mitochondria are damaged, a biological membrane is damaged, and autophagy is initiated, thereby inducing apoptosis and inhibiting tumor formation.

Coix seed: enters the spleen and kidney meridians and also enters the lung, raw coix seed has sweet and light nature and taste and can promote diuresis, pregnant women should use the medicine with cautions, and after stir-frying, the medicine is warm and has strong spleen-tonifying effect. Coix seed, semen Coicis, when used for treating damp-heat syndrome, can achieve both the effects of inducing diuresis and not destroying qi of genuine yin, and can be combined with spleen-invigorating and dampness-eliminating herbs to achieve a quick action. In addition, the coix seeds are the homologous products of medicine and food, have good safety for treating food therapy diseases. The effective component of coix seed, namely the coix seed lactone, has obvious inhibition effect on tumors, and the effect of the coix seed lactone is probably related to the inhibition of new vessels, the regulation of cell growth factors, the interference of growth cycle, the improvement of immune cell level and the like. Through researching the diuresis function of coix seeds on water-loaded rats, the Mongolian cinquefoil herb and the like are proved to have the functions of diuresis and dampness removal mainly through reducing the expression of AQP3 in the stomach and reducing water reabsorption, have good effects on regulating body blood pressure, blood fat and the like, and are helpful for intestinal flora, inflammation diminishing, pain relieving, inhibiting, pigmentation and the like.

Dried orange peel: it enters spleen and lung meridians, and is indicated for adverse qi due to heat in the chest and abdomen, and inducing diuresis. Orange peel is called as tangerine peel for a long time, and is characterized by warming the middle-jiao and moving qi without the worry of dryness-heat and drastic cutting, and the property of the medicine is summarized as bitter and warm orange peel, guiding qi downward and widening diaphragm. Keep white and harmonize stomach, remove white and resolve phlegm ". Hezankun et al studied the effect of pericarpium Citri Reticulatae on gastrointestinal motility by administering pericarpium Citri Reticulatae water extract to rats, and found that gastric acid increase and gastrointestinal contraction promotion in the administered rats. Moreover, the fact that the appetite of rats is dependently increased compared with the content of the tangerine peel decoction found after the Yuan Li and the like irrigate the tangerine peel decoction on young anorexia rats shows that the tangerine peel has the effects of promoting gastric emptying and intestinal peristalsis, improving appetite and the like. In addition, the dried orange peel also has the effects of promoting bile secretion, relaxing sphincter of addison and smooth muscle of bronchus, controlling blood pressure, regulating estrogen metabolism and the like.

Chinese sage herb: the new ginseng decoction pieces describe that the leaves of the Chinese sage herb are purple brown, bitter and cool in taste, and have the effects of activating blood and promoting qi, dispelling wind and relieving pain, carbuncle and swelling, wounds and the like. Li Shizhengyan is mainly used for treating bone pain, wind-evil, carbuncle and swelling. Modern pharmacology proves that the main component of the Chinese sage herb is phenolic acid substances, and the Chinese sage herb contains partial polysaccharides, flavonoids and other substances, and can induce various apoptosis factors and inhibit the proliferation of tumor cells by inhibiting the growth cycle of the cells. Meanwhile, the salvia chinensis can inhibit angiogenesis, reduce blood circulation metastasis, regulate cellular immune signals, maintain internal environment balance, and jointly play a good anti-tumor effect under the action of multiple aspects. Shi Mei is also effective in treating inflammatory diseases, such as chronic gastritis, cholecystitis, hepatitis, etc. by applying anti-inflammatory and anti-oxidative stress to Xiao Jie, and combining Shi with E.

Herba Hedyotidis Diffusae: sweet and cold in nature and slightly bitter in taste, has the functions of clearing heat and promoting diuresis, and removing toxin and carbuncle, enters heart, liver and spleen channels, and is mainly used for treating symptoms such as dyspnea, cough, pharyngalgia, sore, ulcer, stranguria and swelling, venomous snake bite, dysentery, jaundice and the like. Pharmacological research analyzes that the oldenlandia diffusa has better anti-inflammatory, bacteriostatic and antioxidant reaction effects on dysentery bacillus, typhoid bacillus and the like, and is suitable for specific inflammatory diseases such as appendicitis, tracheitis and the like. The oldenlandia diffusa polysaccharides have the functions of improving hematopoiesis and autoimmunity, are helpful for treating leukemia, have the function of resisting chemical mutagenesis, comprise ursolic acid and other terpenoids, have the effective effect on tumor inhibition by various components, regulate and control the immune response and inflammatory response of organisms, and reverse the occurrence of immune escape, and the ethanol extract of the oldenlandia diffusa has certain cytotoxicity on tumor cells, effectively inhibits tumor proliferation through various signal paths, retards the cell growth cycle, induces DNA damage, and relieves the neurotoxicity by flavonoids and terpenoids.

The traditional Chinese medicine composition has the advantages that all the medicines of the traditional Chinese medicine composition can play an important role in digestive tract diseases under the support of modern pharmacology, part of the medicines also have excellent effects on generation and development of tumors, and the six medicines are compatible and formulated, and have effects of monarch, minister, assistant and guide and synergistic effect, so that the effects of replenishing qi to invigorate the spleen, clearing damp and dredging collaterals of CAG are jointly played.

3.2 selection of drugs for control group

Moluodan is a Chinese patent medicine developed by Li Enfu professor of traditional Chinese medicine institute in Hebei province, has the functions of harmonizing the stomach, tonifying the spleen, dredging collaterals and relieving pain, can bidirectionally adjust the gastric electrical amplitude of CAG patients, improves smooth muscle contraction and adjusts gastric dynamics. Moluodan is indicated for spleen deficiency, qi stagnation and stomach collateral stasis, and CAG is manifested by stomach ache, distention and fullness, anorexia, belching, etc. Moluodan is taken orally, mainly metabolized by the liver, and its instruction suggests that adverse reactions are not clear. Reports show that 3 patients with symptoms of weakness, anorexia, jaundice and the like and abnormal liver function occur after taking the Moluodan, and 2 patients are considered to be related to taking the medicine in a dosage exceeding the specification. Professor Tang Xu Dong has found in a multicentre double-blind test that after CAG is treated with Moluo rhodamine, some patients show mild liver enzyme elevation and renal dysfunction, but the statistical significance is not achieved (P0.228 and P1.000), and adverse events such as diarrhea, constipation, dizziness and abdominal distension are also judged to be independent of the drugs, thus indicating that Moluo rhodamine has good safety. Meanwhile, the test indicates that the molodan can effectively relieve and eliminate atrophy (34.6%), intestinal metaplasia (23.0%) and dysplasia (24.6%) of a patient after Hp, and has better curative effect on abdominal pain, eructation and appetite reduction of the patient, and the improvement rate of each symptom is 37-83%. A plurality of clinical observation researches on CAG (camp ischemic necrosis factor) for treating the morrhodin suggest that the effective rate of the morrhodin for treating atrophy is 34-68 percent, the effective rate of the morrhodin for intestinal transformation is 22-66 percent, the difference of clinical and pathological curative effects of the morrhodin treatment is provided, and factors such as the age of a CAG patient, the treatment course and the like in various researches are considered.

3.3 analysis of study results

3.3.1 analysis of the curative effects of the Chinese medicinal composition of the present invention on the clinical symptoms of CAG

The research result shows that the integral of each single symptom of the traditional Chinese medicine composition is obviously reduced compared with that before treatment, and the comparison of clinical curative effects indicates that the traditional Chinese medicine composition has more obvious curative effects. Compared with Moluoda, the traditional Chinese medicine composition has more obvious curative effects on 7 common symptoms of gastrointestinal tract, such as fullness or dull pain in gastric cavity, press preference or warm preference of stomach, loose stool, lassitude and hypodynamia, shortness of breath and no desire to speak, and the like. Compared with the Moluo group before treatment, the Moluo group has better effects of relieving gastral cavity fullness or dull pain, lassitude and hypodynamia, anorexia and epigastric distress after eating, and has no obvious improvement difference on stomach pressing or preferring warmth, loose stool and short breath and no speaking desire.

In the treatment of Chinese patent medicine of the treatise on the consensus opinion on the diagnosis and treatment of chronic atrophic gastritis of the specialized digestive system diseases of the Chinese medical society of Chinese and western medicine in 2017, the syndrome of spleen deficiency and qi stagnation or the syndrome of stomach collateral stasis recommends the use of Jinghua stomach health glue for the syndrome of spleen deficiency and qi stagnation, the syndrome of mixed chills and fever or the syndrome of stomach collateral stasis, the syndrome of liver depression and qi stagnation recommends the use of qi stagnation stomach pain granules, the syndrome of spleen deficiency and qi stagnation or the syndrome of stomach collateral stasis and the use of Moluo Rou and the like. The control group molluo is a large prescription consisting of 18 medicines, has complicated medicine composition, takes stomach harmonizing, spleen tonifying, collateral dredging and pain relieving as a main treatment method, has obvious curative effect on relieving precancerous conditions, has the effects of easing pain, diminishing inflammation, inhibiting bacteria, regulating gastrointestinal smooth muscle, promoting digestion, enhancing gastric mucosa fixation and protection and the like, can effectively relieve symptoms of gastric cavity fullness, pain, gastric upset and the like, promotes gastrointestinal digestion and improves appetite, but no clear report at present indicates that the control group molluo has obvious curative effects on loose stool, hypodynamia, shortness of breath and the like, considers that the control group molluo is related to the formula structure, the formula is mostly clear and moist, does not have the key medicine for tonifying middle-jiao, does not have good effect on regulating intestinal peristalsis, and has no good effect on treating symptoms of loose stool, hypodynamia, shortness of breath and the like. The traditional Chinese medicine composition of the invention, which consists of 6 medicines, is based on replenishing qi and invigorating spleen, astragalus and lucid ganoderma are monarch medicines for reinforcing and invigorating middle-warmer energy, and coix seed and dried orange peel are used for assisting in dispelling and activating water dampness caused by spleen-earth deficiency and dredging qi activity up and down, so that the obstruction caused by the qi deficiency is not caused, and spreading hedyotis herb and Chinese sage herb are special for dissipating stagnation and resisting cancer, so that the whole formula of the traditional Chinese medicine composition has the effects of invigorating spleen and tonifying middle-warmer, dispelling dampness and dissipating stagnation, and has obvious curative effects on symptoms of spleen-stomach deficiency. The traditional Chinese medicine pharmacology of the traditional Chinese medicine composition provided by the invention suggests that quercetin and other components in astragalus root, ganoderma lucidum polysaccharide and coix seed decoction can regulate the immune function and enhance the gastric mucosa protective barrier. Coix seed mainly promotes diuresis and eliminates dampness, and dried orange peel regulates intestinal peristalsis, regulates water and intestinal flora, and can effectively relieve symptoms such as loose stool. Ganoderma, Coicis semen lactone, herba Salviae chinensis, and herba Hedyotidis Diffusae can regulate gastric microenvironment, regulate apoptosis, and inhibit tumor cell formation. In addition, radix astragali and herba Hedyotidis Diffusae can improve hemodynamics and hemopoiesis function, inhibit angiogenesis, and promote atrophy of gland and blood stasis in atrophic region.

In conclusion, although the traditional Chinese medicine composition and the moluodan have different compositions, the traditional Chinese medicine composition is more effective on the symptoms of fullness or dull pain in the gastric cavity, press preference or preference for warmth in the stomach, loose stool, lassitude and hypodynamia, shortness of breath and no speaking desire and the like in clinic.

3.3.2 gastroscope pathological analysis of CAG treated by the Chinese medicinal composition of the invention

The pathological feature of CAG patients is decreased glandular stomach mucosa, and according to the corea cascade, the atrophic state of the stomach mucosa is the initial link in the process of intestinal GC (gastric cancer) lesion. Hp infection is a widely recognized primary causative factor of CAG and even GC, and eradication of Hp is one of the effective methods for treating CAG and even GC. For the Hp negative patients, no special treatment method is provided, and the symptom of the patients is relieved as a main measure, so that the traditional Chinese medicine has a valuable research prospect in treating the Hp negative patients, and can reverse or slow the progress of atrophy. The previous Osmunda japonica research shows that Moluodan is taken for 3 months after the CAG treatment is subjected to basic measures such as Hp quadruple eradication treatment, acid inhibition and stomach protection, and biopsy of tissues of antrum, angle and body of stomach of a gastroscope patient indicates that the atrophy of mucous membrane is better than that before the treatment (P is less than 0.05). The meta-analysis of Liu Feng and so on the curative effect of Moluo Rou on CAG suggests that Moluo Rou obviously improves clinical symptoms such as epigastric pain, warm air, anorexia and so on, the general pathological state and abnormal hyperplasia (P is less than 0.05), but does not obviously change atrophy and intestinal metaplasia (P is more than 0.05). The research result shows that after the treatment course is finished, the total atrophy effective rates of the traditional Chinese medicine composition group and the molhoduo group are similar, namely 61.29% and 50.00% respectively, and no obvious difference exists (P is more than 0.05).

Intestinal Metaplasia (IM) is a pathological state in which a gastric mucosal tissue appears similar to an intestinal epithelial tissue, and can include intestinal Metaplasia and Spasmolytic Polypeptide Expression Metaplasia (SPEM), and according to the suggestion stated in expert consensus on treatment strategies for precancerous and precancerous conditions of gastric mucosa, both gastric mucosal atrophy and intestinal Metaplasia belong to precancerous conditions, and are precancerous pathological changes that can progress to gastric cancer. Research shows that Hp infection is suggested to be the most main pathogenic factor of gastric mucosal lesions such as CAG and the like according to the Sydney system, and follow-up results in ten years after Hp eradication show that gastric mucosal atrophy and activity score are reduced compared with those before treatment, and enterogenesis has no obvious reduction trend, so that IM is generally considered as an irreversible pathological state by modern medicine. The clinical observation shows that the total effective rate of the traditional Chinese medicine composition for treating CAG is 58.06%, the total effective rate of molhodan for intestinal digestion is 34.38%, and no obvious difference exists between the two groups (P is more than 0.05).

Chronic inflammation and activity are both the evaluation criteria for gastric mucositis, where activity is more representative of mucosal inflammation in the acute active phase of the disease. The application of Baoshanliang in researching the difference between the curative effects of Mongolian medicines and Moluodan shows that the chronic inflammation of the gastric mucosa of CAG patients after treatment is improved (P is less than 0.05) compared with that before treatment. The research shows that the effective rate of the traditional Chinese medicine composition is 48.39% and the effective rate of the molhoduon is 3.13% for chronic inflammation, the effective rates of the traditional Chinese medicine composition and the molhoduon are 29.03% and 9.38% respectively for activity, and the difference between the two groups is obvious (P is less than 0.05), which indicates that the traditional Chinese medicine composition has better curative effect than the molhoduon in the aspects of chronic inflammation and activity.

In conclusion, the traditional Chinese medicine composition and the morganan can improve the indexes of pathological atrophy, intestinal metaplasia, chronic inflammation and activity of gastric mucosa, wherein the traditional Chinese medicine composition and the morganan have similar curative effects on the atrophy and the intestinal metaplasia, and the traditional Chinese medicine composition is more effective than the morgana in the aspects of chronic inflammation and activity.

3.3.3 mechanism of the Chinese medicinal composition for treating CAG

As mentioned earlier, p53 can be divided into wild-type and mutant oncogene types, and the normal suppressor wt-p53 is usually present in very low levels in the body due to its unstable configuration and short half-life. Mt-p53 is opposite to wt-p53, and can be accumulated stably for a long time, and is detected by immunohistochemistry method, and the mutated p53 loses the function of regulating cell cycle, and becomes oncogene for inducing tumorigenesis. According to the research result of Liu Xiaojie, the better the differentiation degree of the tumor and the deeper the infiltration, the positive rate of mt-p53 is increased, and the evidence of mt-p53 as an oncogene is further provided. The p53 has strong mutation ability and plays an important role in the processes of apoptosis and tumor development and progression. Therefore, the protein expression relationship between CAG and mt-P53 is further researched by an immunohistochemical method in the research, and the result shows that the MOD values of the two groups of mt-P53 are reduced (P is less than 0.05) after treatment compared with the MOD values before treatment, wherein the MOD values of the traditional Chinese medicine composition are obviously reduced (P is less than 0.05) compared with that of the Moluodan group, and the traditional Chinese medicine composition can obviously inhibit the protein level of mt-P53 compared with Moluodan.

Meanwhile, the MDM2 is used as a negative feedback regulation factor of wt-p53, and the two factors are closely related. When oxidative stress or inflammatory reaction occurs, low-level p53 expression is increased, transcription is combined with DNA, abnormal activity of inflammatory signal systems such as Akt is increased, a negative regulatory factor MDM2 is activated through phosphorylation, the spatial structure of p53 is changed, the negative regulatory factor MDM is combined with an MDM2 catalyst, transcription is induced, p53 is inhibited constitutively, ubiquitination and degradation of the p53 are mediated, the effect of p53 on regulating cell cycle is damaged, cell proliferation is out of control, and further cancer is generated. The research shows that after the treatment course is finished, the MOD value of MDM2 is obviously reduced (P is less than 0.05) compared with that before the treatment, while the MOD value of the traditional Chinese medicine composition is lower (P is less than 0.05) compared with that of the mordanan group, which indicates that compared with the mordanan, the traditional Chinese medicine composition can obviously inhibit the protein level expression of MDM 2.

In conclusion, the Chinese medicinal composition and the morrhodin can effectively reduce the expression levels of mt-p53 and MDM2 proteins, and compared with the two groups, the inhibition effect of the two groups of proteins is more obvious, which indicates that the Chinese medicinal composition has the exact effect of improving CAG gastric mucosal lesion by inhibiting mt-p53 and MDM2 positive expression.

Claims

1. A traditional Chinese medicine composition for influencing the expression level of gastric mucosa oncogenes is characterized by comprising the following components in parts by weight: 3000 portions of astragalus 400-.

2. The traditional Chinese medicine composition for influencing the expression level of the gastric mucosa oncogene as claimed in claim 1, which is characterized by comprising 2500 parts of radix astragali 600-.

3. The composition of claim 2, wherein the composition comprises 1300 parts of Astragalus membranaceus, 900 parts of Ganoderma lucidum, 1800 parts of Coix lacryma-jobi seed, 900 parts of pericarpium Citri Reticulatae, 1800 parts of Salvia chinensis, 1800 parts of herba Hedyotidis Diffusae, and 1800 parts of Ganoderma lucidum.