CN111067891A - Application of sanggenon C in improvement or treatment of pulmonary fibrosis - Google Patents
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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Abstract
The sanggenon C can improve the respiratory function of a mouse after pulmonary fibrosis is induced by bleomycin, can obviously reduce the content of hydroxyproline in the lung, can obviously reduce inflammation and collagen deposition in the lung, and obviously reduce the expression levels of TGF- β 1, alpha-SMA, NF- к Bp65, p-NF- к Bp65 and type I and type III collagen in the lung.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of sanggenon C in improvement or treatment of pulmonary fibrosis.
Background
Pulmonary Fibrosis (PF) refers to injury of alveolar tissue caused by inflammation, excessive deposition of extracellular matrix in alveolar spaces, excessive proliferation of fibroblasts, and irreversible scarring of lung parenchyma, which may be the final result of various Pulmonary interstitial diseases. Pulmonary fibrosis is a relatively refractory group of respiratory diseases, and since efficient gas exchange relies on the transport of oxygen and carbon dioxide molecules through the alveolar epithelium, such inflammation and fibrosis can lead to impaired gas exchange, reduced lung function and lung volume, hypoxemia, dyspnea, cough, and when the condition worsens, respiratory failure is induced.
Pulmonary fibrosis is a common clinical disease, the treatment is troublesome, dyspnea of different degrees is the most common symptom of pulmonary fibrosis, dry cough and fatigue are accompanied, and some patients have clubbed fingers and cyanosis. Serious consequences can lead to structural changes in normal lung tissue and loss of function. The pathological change is that fibroblast abnormally proliferates in the lung and a large amount of extracellular matrix is accumulated with inflammation injury and tissue structure destruction, and normal alveolar tissues are abnormally repaired after being damaged to form scars in the lung. The clinical treatment of most PF patients is controlled by hormone, and the side effect is large.
Currently, there is a lack of effective drugs that have an intervention or therapeutic effect on pulmonary fibrosis. Earlier researches have proved that the cortex mori radicis extract has certain pharmacological performance of improving pulmonary fibrosis of mice induced by bleomycin (Yangfu, Liu Yang, Xuchangjun, and the like. the intervention effect of the medicine on the cortex mori radicis and the radix stemonae extract on pulmonary fibrosis of the mice. the traditional Chinese medicine material 2017, 40(06): 1448-.
Disclosure of Invention
In order to solve the technical problems, the inventor adopts bleomycin to induce the pulmonary fibrosis of the mouse, the moisture content in the lung of the mouse is obviously reduced, the inspiration time and the expiration time are prolonged, and after the intervention of high-purity sanggenon C, the sanggenon C is found to be capable of obviously improving the respiratory function of the mouse after the pulmonary fibrosis is induced by the intratracheal instillation of the bleomycin, enhancing the moisture content in the lung of the mouse and shortening the inspiration time. The pathological observation under HE staining and Masson staining mirrors shows that a large number of lymphocytes in the lungs of a mouse are infiltrated after lung fibrosis, the content of collagen is generally increased, the structure of lung tissue is changed pathologically, a normal alveolar structure is replaced by a large number of abnormally-proliferated collagen tissues, the gas exchange function between alveoli is damaged, after the intervention of sanggenon C, the infiltration of the lymphocytes is reduced, the content of the collagen is reduced integrally, and more residual alveolar structures are generated, so that the gas exchange between the alveoli of the mouse is facilitated, and the ventilation function of the mouse is improved. The hydroxyproline is used as an unnecessary amino acid and is a main amino acid for synthesizing collagen, and after alkaline water method is used for further detecting the content of hydroxyproline in the lung of a mouse, the content of hydroxyproline in the lung of a model group mouse is generally higher, and the content of hydroxyproline in the lung of the mouse is obviously reduced after sanggenon C is subjected to dry treatment, so that the sanggenon C has an obvious effect of antagonizing the formation of collagen induced by bleomycin in the lung fibrosis of the mouse, and the improvement condition of the respiratory function of the mouse after the lung fibrosis and the detection of pathological collagen components can be summarized, and the sanggenon C has a potential pharmacodynamic effect of inhibiting the bleomycin in inducing the lung fibrosis of the mouse. Thus, the present invention has been completed.
In one aspect, the invention provides the use of sanggenon C in the manufacture of a medicament for the amelioration or treatment of pulmonary fibrosis.
Sanggenon C is a component contained in cortex Mori (Morus alba L.) and has effects of purging lung, relieving asthma, inducing diuresis, and relieving swelling, and can be used as quality control standard for quality control of cortex Mori.
In some embodiments of the invention, the improvement or treatment of pulmonary fibrosis is an increase in respiratory function in a patient with pulmonary fibrosis.
In other embodiments of the present invention, the improvement in respiratory function in a patient with pulmonary fibrosis is an increase in tidal volume and/or a decrease in inspiratory time. In some embodiments of the invention, the improvement in respiratory function in a patient with pulmonary fibrosis is an increase in tidal volume and or a decrease in inspiratory time.
In still other embodiments of the present invention, the ameliorating or treating pulmonary fibrosis is reducing the pulmonary organ coefficient of a patient with pulmonary fibrosis.
In still further embodiments of the invention, the amelioration or treatment of pulmonary fibrosis is a reduction in the level of hydroxyproline in the lungs of a patient with pulmonary fibrosis.
In still other embodiments of the present invention, the improvement or treatment of pulmonary fibrosis is a decrease in the level of at least one member selected from the group consisting of A-SMA, NF- к Bp65, p-NF- к Bp65, ColI, and ColIII in the lung of a patient with pulmonary fibrosis.
In still further embodiments of the present invention, the amelioration or treatment of pulmonary fibrosis is a reduction in the degree of pulmonary inflammation and/or the degree of collagen proliferation in a patient with pulmonary fibrosis. In some embodiments of the invention, the improvement or treatment of pulmonary fibrosis is a reduction in the degree of pulmonary inflammation and the degree of collagen proliferation in a patient with pulmonary fibrosis.
In still other embodiments of the invention, the amelioration or treatment of pulmonary fibrosis is a reduction in the expression of TGF- β 1 protein in the lung tissue of a patient with pulmonary fibrosis.
In a second aspect, the invention provides the use of an agent which inhibits the overexpression of TGF- β 1, and/or reduces the expression of the inflammatory transcription factor NF- к B and its phosphorylation level, in the manufacture of a medicament for the amelioration or treatment of pulmonary fibrosis.
In some embodiments of the invention, the reduction in expression of the inflammatory transcription factor NF- к B refers to a reduction in expression level of NF- к Bp65 and the reduction in phosphorylation level refers to a reduction in p-NF- к Bp65 level.
In some embodiments of the invention, the agent is sanggenon C.
The invention has the advantages of
Compared with the prior art, the invention has the following beneficial effects:
the invention provides the application of sanggenon C in preparing a medicament for improving or treating pulmonary fibrosis diseases, and has great clinical value.
The sanggenon C can obviously improve the respiratory function of mice after pulmonary fibrosis caused by intratracheal instillation of bleomycin, enhance the moisture capacity in the lungs of the mice and shorten the inspiration time.
Morusinone C can obviously reduce the content of hydroxyproline in the lung, can obviously reduce inflammation and collagen deposition in the lung, and obviously reduces the expression levels of TGF- β 1, alpha-SMA, NF- к Bp65, p-NF- к Bp65, type I collagen and type III collagen in the lung, has high medical value and wide application prospect.
Drawings
FIG. 1 shows the effect of sanggenon C on pulmonary alpha-SMA, NF- к B P65, P-NF- к B P65, ColI, ColIII protein expression in mice with pulmonary fibrosis,. P <0.05,. P <0.01 vs. sham group, # P <0.05, # P <0.01 vs. model group.
FIG. 2 showsHE staining was performed: sanggenon C affects the degree of inflammation in pulmonary tissues of pulmonary fibrosis mice (× 200). A: a sham operation group; b: a model group; c: sanggenon C50 mg/kg-1(ii) a D: sanggenon C100 mg/kg-1。
Figure 3 shows Masson staining: sanggenon C affects the extent of collagen proliferation in lung tissue in pulmonary fibrosis mice (× 100). A: a sham operation group; b: a model group; c: sanggenon C50 mg/kg-1(ii) a D: sanggenon C100 mg/kg-1。
FIG. 4 shows the effect of sanggenon C on the expression of TGF- β 1 protein in lung of mice with pulmonary fibrosis by immunohistochemical staining (X200). A: sham operation group, B: model group, C: sanggenon C50 mg/kg-1(ii) a D: sanggenon C100 mg/kg-1。
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments.
Examples
The following examples are used herein to demonstrate preferred embodiments of the invention. It will be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function in the invention, and thus can be considered to constitute preferred modes for its practice. Those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit or scope of the invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the disclosures and references cited herein and the materials to which they refer are incorporated by reference.
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
The experimental procedures in the following examples are conventional unless otherwise specified. The instruments used in the following examples are, unless otherwise specified, laboratory-standard instruments; the test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified.
Example Effect of sanggenon C on improvement of pulmonary fibrosis in mice induced by bleomycin
1 materials and methods
1.1 materials
1.1.1 Experimental animals
SPF grade C57BL/6 mouse 80 was purchased from Changsha Tianqin biotechnology Limited under the condition of male and female half, body mass (20 + -2) g, and animal feeding license was SCXK (Xiang) 2019-.
1.1.2 drugs and reagents
Sanggenone C (Sanggenon C, purity 98%, Doudster Biotech Co., Ltd.), bleomycin (Shanghai Locaench chemical Co., Ltd.), xylene and absolute ethyl alcohol (analytical purity, Tianjin Kemikoohu chemical reagents Co., Ltd.), glass slide and cover glass (Jiangsutai laboratory instruments Co., Ltd.), β -Actin antibody (ab8226), Transforming growth factor β (Transforming growth factor β, TGF- β) antibody (ab92486), alpha-smooth muscle Actin (ab32575) antibody, Nuclear transcription factor к B p65(Nuclear transcription factor к B p65, NF- к B p65) antibody (16502), Collagen (Collagen I ) antibody (Colab 710), Collagen (Collagen III) (SDS 3578, Japan Biochemical reagents L-PAGE, SDS-3578), Collagen (Collagen II) antibody (SDS-357726), Biochemical reagents L-SDS-PAGE, SDS-3578, Biochemical reagents L-PAGE, SDS-357726, Biochemical reagents L-PAGE, SDS-3578, and Biochemical reagents L (Biochemical reagents L-PAGE), Biochemical reagents L-PAGE, SDS-357726, SDS-PAGE, Biochemical reagents L-PAGE, SDS-9, Biochemical reagents L-PAGE, SDS-K, SDS-9, Biochemical reagents L-Biochemical reagents (Biochemical reagents L-K, Biochemical reagents L-SDS-Biochemical reagents L-9, Biochemical reagents L, IncTMAnimal cell/tissue total protein extraction kit (Beijing English special Biotechnology, Inc.); micro BCA protein quantitative kit (Beijing kang century Biotechnology Co., Ltd.)) (ii) a PVDF membrane (0.2 μm, Millipore Corp.); PV-9000 immunohistochemical kit and DBA developer (gold bridge Biotechnology Co., Ltd., China fir, Beijing); skim milk powder (BD corporation); chloral hydrate (national pharmaceutical group chemical agents limited); physiological saline (Shandong Qilu pharmaceutical group, Inc.); purified water (Jiangshan Wahaha hongzhen drinking water, Inc.); hydroxyproline kit (base hydrolysis method, Nanjing institute of bioengineering).
1.1.3 instruments
WBP animal noninvasive Lung function breath detection System (Shanghai Tawang Intelligent science and technology Co., Ltd.), PowerPACbasic electrophoresis apparatus and ChemiDoc XRS gel imaging automatic analyzer (BIO-RAD Co.). Immunohistochemical imaging system (OLYMPUS), immunohistochemical professional image analysis software (Media Cybernetics).
1.2 methods
1.2.1 preparation and grouping of bleomycin-induced mouse pulmonary fibrosis model
The random digital table method of SPF grade C57BL/6 mouse is divided into 20 false operation groups and 60 model groups, normal saline is dissolved to prepare chloral hydrate into 4% concentration solution for mouse abdominal cavity injection anesthesia, iodophor alcohol is used for disinfecting neck skin, the neck skin is cut off, the tissue in front of the neck is carefully stripped to avoid bleeding, and the air outlet pipe is carefully separated. Model group 60 mice C57BL/6 were all intratracheally injected with bleomycin 5 mg/kg dissolved in 0.1mL physiological saline-1(ii) a Sham group 20 mice were all intratracheally injected with 0.1mL of physiological saline. After injection, the mice quickly rotate in an inverted manner, bleomycin injection or normal saline is uniformly mixed in lung tissues, after postoperative mice are kept warm and revived, the mice are normally fed with water for continuous feeding for 3 days, and 60 model mice are randomly divided into a model group, a model and sanggenon C100mg kg-1Group sum model + sanggenon C50 mg/kg-1Groups of 20 pieces each.
And 4d, beginning a sham operation group and a model group, performing intragastric administration and oral administration of purified water, dissolving and suspending 0.1% sodium carboxymethylcellulose prepared by purified water in a medicine drying group C, performing intragastric administration and oral administration, continuously administering for 28d, wherein the animal drinking water and diet during administration meet the animal ethical specifications of Guizhou Chinese medicine university, after 1h of final administration, randomly extracting 10 mice in each group to detect respiratory function, then removing necks, killing left lungs, extracting left lungs, using the left lungs to detect hydroxyproline content by using a hydroxyproline kit, using right lungs to detect alpha-SMA, NF- к B p65, p-NF- к B p65, ColI and ColIII protein expression by using an immune protein blotting method, rapidly killing the left lungs, extracting HE, observing inflammatory reaction by staining and detecting collagen proliferation by using Masson, and detecting TGF- β 1 protein expression by using a lung immunohistochemistry method.
1.2.2 pulmonary fibrosis mouse respiratory function detection and organ coefficient analysis
The mouse is placed in a closed container attached to a WBP animal noninvasive lung function respiration detection system, parameter setting is adjusted, animal adaptation is carried out for 10min, animal Tidal Volume (TVB), inspiration time (Ti) and expiration time (Te) are monitored and recorded, and then statistical analysis is carried out. The animals were sacrificed by removing the neck, the lungs were harvested, weighed and the organ coefficients were counted and calculated. Organ coefficient ═ lung weight (mg)/body weight (g)
1.2.3 determination of hydroxyproline content by alkaline hydrolysis
And (3) putting tissues into a test tube according to the requirements of the kit, adding 1mL of hydrolysate, hydrolyzing in a boiling water bath for 20min, adding 10 mu L of indicator, adjusting the pH value to about 6.0, adding 10mL of purified water, uniformly mixing and diluting, adding 20mg of activated carbon into 3mL of diluted hydrolysate, centrifuging at 3500rpm for 10min, and taking the 550nm position of the supernatant for detecting the absorbance value.
1.2.4 detection of protein expression of alpha-SMA, NF- к B p65, p-NF- к B p65, ColI and ColIII by immunoblotting
Extracting total protein from each group of right lungs by adopting a column centrifugation method, carrying out total protein quantification by adopting a BCA method protein quantification kit microplate detection method, preparing 12% separation gel and 5% concentrated gel according to SDS-PAGE gel preparation kit instructions, carrying out 80V electrophoresis on the concentrated gel for about 30min, carrying out 120V electrophoresis on the separation gel for about 1h, soaking a PVDF membrane in methanol for 5min, carrying out 60V electrotransformation for 2h, sealing 5% skimmed milk powder for 1h, adding I antibody, 1:8000, other I antibodies, carrying out incubation at 4 ℃ overnight, washing 3 times with TBST, adding II antibody, washing 3 times with TBST, developing 3 times with ECL developer, analyzing the grey value of the result, and repeating the experiment for 3 times.
1.2.5 HE staining and Masson staining
Fixing each group of left lung with 4% paraformaldehyde for 24h, washing with tap water, dehydrating by gradient from low concentration to high concentration alcohol for 1h, respectively, performing xylene transparence for 20min, performing paraffin immersion embedding on the tissue, slicing the wax block with the thickness of 4 μm after cooling at room temperature, drying the slices at 37 ℃, performing xylene dewaxing, dehydrating by high concentration to low concentration alcohol, performing hematoxylin staining for 10min, performing tap water bluing for 5min multiplied by 3 times, performing eosin staining for 30s, performing xylene immersion for 5min after dehydrating by low concentration to high concentration alcohol, and observing and evaluating the inflammation degree change of the lung tissue by microscopic examination of a neutral gum sealing sheet. According to the Szapiel pathological evaluation method: 0 is classified as non-alveolar inflammation; 1 is divided into mild alveolitis, and the lesion range is less than or equal to 20 percent of the whole lung; 2, moderate alveolitis, wherein the lesion range accounts for 20 to 50 percent of the whole lung; 3, the lung is classified as severe alveolitis, the lesion range is larger than or equal to 50 percent of the whole lung, and the structure is changed; dewaxing the section by dimethylbenzene, dehydrating by high-concentration to low-concentration alcohol, dyeing by Masson collagen staining reagent, soaking in dimethylbenzene for 5min after dehydrating by high-concentration alcohol, sealing by neutral gum, observing by microscopic examination, and evaluating the change of the collagen proliferation degree of lung tissues. According to the Szapiel pathological evaluation method: 0 is no fibrosis; 1, mild fibrosis is obtained, and the lesion range is less than or equal to 20% of the whole lung; 2, moderate fibrosis is divided, and the range of pathological changes accounts for 20 to 50 percent of the whole lung; 3, severe fibrosis, lesion range of not less than 50% of the whole lung, and structural change.
1.2.6 immunohistochemical method for detecting TGF- β 1 protein expression
And performing conventional dewaxing and hydration tissue section on each group of right lung paraffin sections, performing operation according to the specification of a PV-9000 kit, sealing for 20min by 3% hydrogen peroxide, washing for 3min × 3 times by using PBS (phosphate buffer solution), then dropwise adding I antibody, the concentration is 1:100, incubating overnight at 4 ℃, then washing for 3min × 3 times by using the PBS buffer solution, dropwise adding II antibody, incubating at room temperature for 20min, washing for 3min × 3 times by using the PBS buffer solution, developing DAB (digital audio broadcasting), washing with tap water, performing hematoxylin counterstaining, dehydrating, transparence and mounting, observing brown yellow particles under a mirror to obtain positive expression, and analyzing and counting the average light density value.
1.2.7 data processing
SPSS20.0 statistical software is adopted to analyze the significance of the data, single-factor analysis of variance is adopted to analyze the data, and the statistical difference exists when P is less than 0.05.
2 results
2.1 Effect of sanggenon C on bleomycin-induced pulmonary fibrosis mouse respiratory function
The results in Table 1 show that the model group mice had significantly limited respiratory function, decreased tidal volume, and prolonged inspiratory and respiratory time compared to the sham group. Sanggenon C (50, 100 mg/kg)-1) The mice in the group have better respiratory function performance, although the expiration time (Te) has no significant difference with the model group, the Tidal Volume (TVB) is obviously increased, the inspiration time (Ti) is shortened, and the difference with the model group has statistical significance (P)<0.01，P<0.05)。
TABLE 1 influence of sanggenon C on respiratory function in mice with pulmonary fibrosis: (
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
2.2 influence of Sanggenone C on Lung organ coefficients of pulmonary fibrosis mice
The results in Table 2 show that the lung organ coefficient of the mice in the model group is obviously increased compared with that in the sham operation group. Sanggenon C (50, 100 mg/kg)-1) The lung organ coefficient of the mice in the group is obviously reduced, and the difference has statistical significance (P) compared with the model group<0.01，P<0.05)。
TABLE 2 influence of sanggenon C on pulmonary organ coefficients in pulmonary fibrosis mice: (
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
2.3 Effect of Sanggenone C on the content of hydroxyproline in the Lung of mice with pulmonary fibrosis
The results in Table 3 show that the content of hydroxyproline in the lung of the mice in the model group is obviously increased (P) compared with that in the sham operation group<0.01). Sanggenon C (50, 100 mg/kg)-1) The content of hydroxyproline in the lung of the mice in the group is obviously reduced, and the difference has statistical significance (P) compared with the model group<0.01)。
TABLE 3 Effect of sanggenon C on the content of hydroxyproline in the lungs of mice with pulmonary fibrosis: (
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
2.4 influence of Morusinone C on pulmonary alpha-SMA, NF- к B p65, p-NF- к B p65, ColI and ColIII protein expression in pulmonary fibrosis mice
Table 4 and FIG. 1 show that the expression of the proteins alpha-SMA, NF- к B P65, P-NF- к Bp65, ColI and ColIII in the mice of the model group is obviously increased (P-NF- к Bp65, ColI and ColIII) compared with the sham operation group<0.01). Sanggenon C (50, 100 mg/kg)-1) The content of proteins of alpha-SMA, NF- к B P65, P-NF- к B P65, ColI and ColIII in mice in the group is obviously inhibited, and the difference has statistical significance (P) compared with a model group<0.01)。
TABLE 4 influence of sanggenon C on pulmonary alpha-SMA, NF- к B p65, p-NF- к B p65, ColI, ColIII protein expression in pulmonary fibrosis mice ((III))
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
2.5 Effect of Sanggenone C on the degree of inflammation and collagen proliferation in the Lung of mice with pulmonary fibrosis
The results in Table 5, FIG. 2, and FIG. 3 show that the sham group showed no inflammation around the alveoli and bronchioles, only a small amount of collagen, intact alveolar structures, and no bleedings from the alveoli. Compared with the sham operation group, the pulmonary alveolar structure in the pulmonary alveoli of the model group disappears, the trachea is closed, a large number of lymphocytes invade, and collagen is greatly proliferated around the trachea and the pulmonary alveoli, so that the normal pulmonary alveolar structure disappears or is adhered. Sanggenon C (50, 100 mg/kg)-1) The pulmonary alveolus structure in the lung of the mice in the group is relatively complete, and although part of lymphocytes invade around the bronchioles and collagen abnormally proliferates, compared with the model group, the inflammation degree and the collagen proliferation degree are obviously insufficient.
TABLE 5 influence of sanggenon C on the extent of inflammation and collagen proliferation in pulmonary tissues of pulmonary fibrosis mice: (
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
2.6 Effect of Sanggenone C on the expression of TGF- β 1 protein in Lung of mice with pulmonary fibrosis
The results in Table 6 and FIG. 4 show that the average optical density of TGF- β 1 protein is lower in the sham group, and that the average optical density of TGF- β 1 protein in the model group is lower than that in the sham groupShow an increase in the difference (P)<0.01). Sanggenon C (50, 100 mg/kg)-1) The expression of the TGF- β 1 protein mean optical density value in the lung of the group mice is obviously inhibited, and the difference has statistical significance compared with the model group (P)<0.01)。
TABLE 6 Effect of sanggenon C on TGF- β 1 protein expression in pulmonary tissues of pulmonary fibrosis mice (S) ((S))
n＝10)
*P<0.05，**P<0.01vs sham group;#P<0.05，##P<0.01vs model set.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.
Claims (10)
1. Use of sanggenon C in the manufacture of a medicament for the amelioration or treatment of pulmonary fibrosis.
2. The use of claim 1, wherein the improvement or treatment of pulmonary fibrosis is an increase in respiratory function in a patient with pulmonary fibrosis.
3. The use of claim 2, wherein the improvement in respiratory function in a patient with pulmonary fibrosis is an increase in tidal volume and/or a decrease in inspiratory time.
4. The use of claim 1, wherein the improvement or treatment of pulmonary fibrosis is a reduction in the pulmonary organ coefficient of a patient with pulmonary fibrosis.
5. The use of claim 1, wherein the improvement or treatment of pulmonary fibrosis is a reduction in the level of hydroxyproline in the lungs of a patient with pulmonary fibrosis.
6. The use of claim 1, wherein the amelioration or treatment of pulmonary fibrosis is a reduction in lung content of a patient with pulmonary fibrosis of at least one member selected from the group consisting of a-SMA, NF- к Bp65, p-NF- к Bp65, Col i, Col iii.
7. The use of claim 1, wherein the amelioration or treatment of pulmonary fibrosis is a reduction in the degree of pulmonary inflammation and/or the degree of collagen proliferation in a patient with pulmonary fibrosis.
8. The use of claim 1, wherein the amelioration or treatment of pulmonary fibrosis is a reduction in the expression of TGF- β 1 protein in the lung tissue of a patient with pulmonary fibrosis.
9. The application of the preparation for inhibiting the over-expression of TGF- β 1 and/or reducing the expression and phosphorylation level of an inflammatory transcription factor NF- к B in the preparation of a medicament for improving or treating pulmonary fibrosis.
10. The use according to claim, wherein the agent is sanggenon C.
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Application publication date: 20200428 |