CN109528815A - A kind of method for building up of asthenic symptoms tumor cachexia model - Google Patents
A kind of method for building up of asthenic symptoms tumor cachexia model Download PDFInfo
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Abstract
The present invention provides a kind of method for building up of asthenic symptoms tumor cachexia model.This method includes, at the same under being rushed down using bitter cold, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, induce 7-15 days；To obtained chronic diseases marked by deficiency of vital energy mouse inoculation C26 colon adenocarcinoma cell, asthenic symptoms tumor cachexia model is obtained；After inoculation simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 15-18 days.Wherein, weight, chest gland weight, spleen weight, gastrin content etc. is selected to be used as chronic diseases marked by deficiency of vital energy observation index.It can use the Research of Animal Model for Study chronic diseases marked by deficiency of vital energy tumor cachexia of above method foundation or the drug for the treatment of chronic diseases marked by deficiency of vital energy tumor cachexia screened.
Description
Technical field
The invention belongs to medical care evaluations, detection technique field, and in particular to a kind of for asthenic symptoms tumor cachexia model
Method for building up, the model which establishes can be used for studying chronic diseases marked by deficiency of vital energy cachexia or the screening treatment cachectic medicine of asthenic symptoms
Object.
Background technique
Malignant tumour has become the disease for endangering human physical and mental health's most serious and is on the rise, no matter in prosperity
Country or developing country, malignant tumour are all to cause one of the front three cause of the death of 5 years old or more human mortality.It wherein influences swollen
One major reason of tumor survival of patients is that in the course of disease later period tumor cachexia (cancer occurs for most of tumor patient
Cachexia) phenomenon.Cachexia (cachexia) is also known as wasting syndrome, is a kind of serious organism metabolic disorder, main table
Now for muscle, fat forfeiture and with weight loss, fatigue and weakness.Tumor cachexia be malignant tumour it is common it is lethal because
Element, and clinical therapeutic efficacy is directly affected, cause complication to increase, patients ' life quality declines, short survival, in hospital day
Number extends and medical expense increases.It is reported according to clinical medicine, in the terminal stage of a disease cachexia occurs for the cancer patient of 50-80%, because
Having 20% people in the patient of tumor mortality is to die of tumor cachexia.Therefore, cachectic prevention and treatment of malignant tumor patient has been
Important component as the treatment of malignant tumour multidisciplinary synthesis.But cachectic pathomechanism is also imperfectly understood, needle
The research for carrying out drug development for cachexia is even more breakthrough as a result, controlling that specific for tumor is not cachectic not yet
Treat drug.Current clinical common method for the treatment of is palliative treatment (nutritional support), i.e., carries out appetite treatment using hormone, and auxiliary
With physical exercise and psychological consultation etc., achievees the purpose that put on weight, stimulate appetite.Clinical application is the results show that these means
Still it is difficult to reach very effective therapeutic purposes.
It is worth noting that, the clinical practice result prompt traditional Chinese medicine therapy system in China has preferably tumor cachexia
Therapeutic effect.Tumor cachexia has no corresponding name of disease in traditional Chinese medicine, is generally belonged to it according to its clinical manifestation " empty
Labor " scope." consumptive disease " is most early in proposition in " Synopsis Golden Chamber ", it is believed that its pathomechanism fallen ill is that organ yin-yang qi and blood is deficient.
It is weakened body resistance for carcinoma morbidity it is basic, the malicious stasis of blood and to deposit be pathogenic factor that carcinoma occurs.Consumptive disease is mostly by gradually on the whole body is thin long for disease
Cry " void ", perennial and irrecoverable weakness damages pole and does not call " labor " again " damage ", because of cult poison sparrow hawk, caused by healthy tendency loss, at this point, attack must not, mend
Not by.This theory matches with the generating process of tumor cachexia.Cachectic 50-80% patient occurs in cancer patient
Its constitution has its particularity certainly, these patients are likely to void constitution, and void constitution induces under the pressure of neoplastic disease
Consumptive disease, that is, cachexia.In recent years, Chinese medicine worker is based on cachectic asthenic symptoms table according to the syndrome analysis to tumor cachexia
Existing, the angles different from righting, QI invigorating, invigorating the spleen etc. are started with, and are used Chinese herb prevention to cachexia, are achieved relatively satisfactory curative effect.
These results have prompted existing possibility correlation between tumor cachexia and traditional Chinese medicine deficiency-syndrome and have established corresponding asthenic symptoms tumour evil
The feasibility and necessity of sick matter disease binding model.By the swollen of traditional asthenic symptoms syndrome model and current international endorsement in the present invention
Tumor cachexia models coupling, establishes disease binding model, and the model established will can be used for the pathological study of tumor cachexia
And related drugs screening.
Summary of the invention
In asthenic symptoms tumor cachexia model foundation of the present invention, asthenic symptoms mouse model is initially set up, then to asthenic symptoms mouse mould
Type and tumor cachexia model, which are overlapped, realizes Disease Syndrome integrated animal model.The present invention reaches disease according to " disease after first demonstrate,proving "
In conjunction with Research Thinking, it is determined that the production method of asthenic symptoms tumor cachexia disease binding model.Using three factor methods, (bitter cold is rushed down
Under, irregular diet, exhausted movemeat) establish mouse asthenic symptoms state, and select weight, chest gland weight, spleen weight, gastrin (GAS-17)
Content etc. is used as chronic diseases marked by deficiency of vital energy observation index；Tumor cachexia model is prepared using C26 adenocarcinoma of colon inocalation method, and chooses tumour malignant disease
Qualitative correlation biological indicator changes sensitization time as materials time point.
According to above-mentioned theory, the present invention provides a kind of method for building up of asthenic symptoms tumor cachexia model comprising as follows
Step:
(1) simultaneously using bitter cold rush down under, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, lure
It leads 7-15 days；
(2) to chronic diseases marked by deficiency of vital energy mouse inoculation C26 colon adenocarcinoma cell obtained in step (1), asthenic symptoms tumor cachexia mould is obtained
Type；
(3) be inoculated with after simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 15-18 days.
In the present invention,
Mouse used is preferably BALB/c male mice, and 8 week old, weight is about 24 ± 2g.
Bitter cold rushes down lower revulsion are as follows: daily morning timing (when such as 7-9) stomach-filling cassia angustifolia leaf decoction, preferably dosage are
0.5~0.7mL.The cassia angustifolia leaf decoction is added water to cook to obtain by folium sennae, the decocting to 1mL kinds of acquisition of every 1g folium sennae crude drug
Rush down leaf decoction.
Irregular diet revulsion are as follows: the next day feed, free water.
Exhausted movemeat revulsion are as follows: daily timing in afternoon (when such as afternoon 1) carries out running training or swimming instruction to mouse,
It forces mouse running to reach power and exhausts state.
Preferably, running training carries out (the rotary-type tired instrument of such as YLS-10B type mouse) using the rotary-type tired instrument of mouse；
Moreover, because mouse has the learning behavior escaped and shocked by electricity on rotary-type tired instrument, more preferably realize that power exhausts using swimming instruction
Exercise induced method.
Reach power using running training and exhaust state, the power standard of exhausting is tired instrument (such as rotary-type fatigue of YLS-10B type mouse
Instrument) revolving speed setting rest 15 times in 30r/min, mouse 30min, each time of having a rest in 30s or more, can be judged as that power exhausts
State.
Reach power using swimming instruction and exhaust state, it is that mouse performance is flurried, major beat is uncoordinated even that power, which exhausts standard,
There is sinkage, daily power exhausts 2 times, is spaced 10min.
As a preferred technical solution,
Bitter cold is rushed down in lower revulsion, and certain adaptability is had under rushing down due to mouse to bitter cold, therefore can be given in early period
Lower cassia angustifolia leaf decoction dosage is given, such as 0.5mL, every day or every 2 days or more improve the cassia angustifolia leaf decoction dosage later.
In exhausted movemeat revulsion, power being reached using swimming instruction and exhausts state, swimming instruction preferably uses swimming with a load attached to the body method,
Make mouse tail weight bearing mouse weight 5%, forced swimming in 27-30 DEG C of water temperature.
Vaccination ways in step (2) are preferably mouse oxter inoculation C26 colon adenocarcinoma cell, C26 colon adenocarcinoma cell
It is 1 × 10 with normal saline dilution to concentration5-2×105A cell/mL, dosage of inoculation 0.1-0.2mL/ are only.
The present invention also provides a kind of method for building up of more preferably asthenic symptoms tumor cachexia model comprising following step
It is rapid:
(1) under being rushed down using bitter cold, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, induction 10
It；
(2) to chronic diseases marked by deficiency of vital energy mouse inoculation C26 colon adenocarcinoma cell；
(3) be inoculated with after simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 16 days；
Wherein,
Mouse uses BALB/c male mice, 8 week old, 24 ± 2g of weight；
Bitter cold rushes down lower revulsion: the 1st~16 day, daily morning timing fed cassia angustifolia leaf decoction 0.5mL (every 1g (when such as 8)
Folium sennae crude drug extracts to obtain 1mL cassia angustifolia leaf decoction), whens the 17th day~26 days daily morning 8, feeds cassia angustifolia leaf decoction 0.7mL
(every 1g folium sennae crude drug extracts to obtain 1mL cassia angustifolia leaf decoction)；
Irregular diet revulsion: the next day fasting, free water；
Exhausted movemeat revulsion: when daily afternoon 1, in 27-30 DEG C of water, weight bearing 5% swimming in tail portion is carried out to mouse and is instructed
Practice, forces mouse running to reach power and exhaust state；It is that mouse performance is flurried, major beat is uncoordinated or even occurs that power, which exhausts judgment criteria,
Sinkage, daily power exhaust 2 times, are spaced 10min；
Vaccination ways in step (2) are that mouse oxter is inoculated with C26 colon adenocarcinoma cell, the life of C26 colon adenocarcinoma cell
It is 1 × 10 that reason salt water, which is diluted to concentration,5A cell/mL, dosage of inoculation 0.1mL/ are only.
The invention further relates to use the model discrimination established according to the method for building up of above-mentioned asthenic symptoms tumor cachexia model
Method for treating the drug of chronic diseases marked by deficiency of vital energy tumor cachexia, this method comprises:
A) model is divided into blank control group, drug control group；
B) drug to be screened is administered to different drug control groups with therapeutically effective amount respectively, blank control group is not given
Medicine；
C) after an effective treatment cycle is administered, weight, the gastrocnemius weight, epididymis rouge of the model in different groups are checked
The variation of fat weight, spleen weight, chest gland weight or gastrin (GAS-17) content's index, exists according to drug control group and blank control group
The significant statistical difference in more than one index in above-mentioned six indexs is screened for treatment chronic diseases marked by deficiency of vital energy tumor cachexia
Drug.
The invention further relates to the models established according to the above-mentioned method for building up for asthenic symptoms tumor cachexia model to sieve
Select the purposes in the drug for treatment chronic diseases marked by deficiency of vital energy tumor cachexia.
The present invention is by observation chronic diseases marked by deficiency of vital energy tumor cachexia model mice in weight, gastrocnemius weight, epididymal adipose tissues weight, spleen
The variation of the indexs such as weight, chest gland weight, gastrin (GAS-17) content, establishes the appraisement system of the model.
The present invention can use the Research of Animal Model for Study chronic diseases marked by deficiency of vital energy tumor cachexia of above method foundation or swollen to the treatment chronic diseases marked by deficiency of vital energy
The cachectic drug of tumor is screened.
Detailed description of the invention
Fig. 1 is the mouse weight curve graph of Preparative Example 1.A) weight of chronic diseases marked by deficiency of vital energy group is significantly lower than in Preparative Example 1
Blank control group, B) changes of weight rate in Preparative Example 1, blank control group weight is gradually increasing, under chronic diseases marked by deficiency of vital energy group continued weight
Drop, the phase shows significant difference (p < 0.01 * *) after the test.
Fig. 2 is the mouse gastrin content histogram of the mouse chronic diseases marked by deficiency of vital energy method of Preparative Example 1.The chronic diseases marked by deficiency of vital energy in Preparative Example 1
Gastrin (GAS-17) content of group is lower than blank control group (p > 0.05).
Fig. 3 is the mouse spleen weight and index and spleen index histogram of Preparative Example 1.A) chronic diseases marked by deficiency of vital energy group spleen in Preparative Example 1
Dirty weight is substantially less than blank control group, B) chronic diseases marked by deficiency of vital energy group index and spleen index is substantially less than blank control group in Preparative Example 1
(***p<0.001)。
Fig. 4 is the mouse thymus weight and thymus index histogram of the mouse chronic diseases marked by deficiency of vital energy method of Preparative Example 1.A) preparation is implemented
The thymic weight of chronic diseases marked by deficiency of vital energy group is substantially less than blank control group, B in example 1) thymus index of chronic diseases marked by deficiency of vital energy group is significantly low in Preparative Example 1
In blank control group (p < 0.001 * * *).
Fig. 5 is the mouse weight temperature curve figure of embodiment 1.A) chronic diseases marked by deficiency of vital energy group, tumor cachexia group and the chronic diseases marked by deficiency of vital energy in embodiment 1
The weight of tumor cachexia group is significantly lower than blank control group；Chronic diseases marked by deficiency of vital energy tumor cachexia group is substantially less than in morbidity latter stage weight
Chronic diseases marked by deficiency of vital energy group.B) chronic diseases marked by deficiency of vital energy and chronic diseases marked by deficiency of vital energy cachexia group body temperature are significantly lower than blank control group in embodiment 1, and chronic diseases marked by deficiency of vital energy cachexia group is being sent out
Sick latter stage body temperature is significantly lower than chronic diseases marked by deficiency of vital energy group.(* chronic diseases marked by deficiency of vital energy cachexia group morbidity latter stage p < 0.05 compared with chronic diseases marked by deficiency of vital energy group；* chronic diseases marked by deficiency of vital energy malignant disease
Matter group morbidity latter stage p < 0.01 compared with chronic diseases marked by deficiency of vital energy group；P < 0.05 compared with blank control group #；## compared with blank control group p <
0.01)。
Fig. 6 is the mouse gastrocnemius weight and epididymal adipose tissues weight histogram of embodiment 1.A) chronic diseases marked by deficiency of vital energy group gastrocnemius in embodiment 1
It is substantially less than blank control group again, chronic diseases marked by deficiency of vital energy tumor cachexia group gastrocnemius is significantly lower than chronic diseases marked by deficiency of vital energy group and tumor cachexia group again.B)
Chronic diseases marked by deficiency of vital energy group epididymal adipose tissues are lower than blank control group again in embodiment 1, and chronic diseases marked by deficiency of vital energy tumor cachexia group epididymal adipose tissues are substantially less than void again
Disease group.(p < 0.001 * p < 0.05, * * *).
Fig. 7 is the mouse spleen weight and index and spleen index histogram of embodiment 1.A) chronic diseases marked by deficiency of vital energy group spleen weight is significant in embodiment 1
Lower than blank control group, chronic diseases marked by deficiency of vital energy cachexia group and tumor cachexia group.B) chronic diseases marked by deficiency of vital energy group index and spleen index is substantially less than sky in embodiment 1
White control group, chronic diseases marked by deficiency of vital energy cachexia group and tumor cachexia group (p < 0.001 * p < 0.05, * * p < 0.01, * * *).
Fig. 8 is the mouse thymus weight and thymus index histogram of embodiment 1.A) chronic diseases marked by deficiency of vital energy group chest gland weight is significant in embodiment 1
Lower than blank control group, chronic diseases marked by deficiency of vital energy cachexia group chest gland weight is lower than chronic diseases marked by deficiency of vital energy group and tumor cachexia group.B) chronic diseases marked by deficiency of vital energy group chest in embodiment 1
Gland index is significantly lower than blank control group, and chronic diseases marked by deficiency of vital energy cachexia group thymus index is lower than chronic diseases marked by deficiency of vital energy group and tumor cachexia group, (* p <
0.05, * p < 0.001 * p < 0.01, * * *).
Fig. 9 is the mouse weight and temperature curve figure of embodiment 2.A) chronic diseases marked by deficiency of vital energy tumor cachexia group weight is aobvious in embodiment 2
It writes and is lower than blank control group, chronic diseases marked by deficiency of vital energy tumor cachexia merges PDTC treatment group (being chronic diseases marked by deficiency of vital energy tumor cachexia group+PDTC in figure) and exists
The weight in experiment later period is significantly higher than chronic diseases marked by deficiency of vital energy tumor cachexia group.B) chronic diseases marked by deficiency of vital energy tumor cachexia group body temperature is significantly low in embodiment 2
In blank control group, the body temperature of chronic diseases marked by deficiency of vital energy tumor cachexia merges PDTC treatment group phase after the test is significantly higher than chronic diseases marked by deficiency of vital energy tumour malignant disease
Matter group.(## chronic diseases marked by deficiency of vital energy tumor cachexia group p < 0.01 compared with blank control group；### chronic diseases marked by deficiency of vital energy tumor cachexia group and blank control
Group compares p < 0.001；* chronic diseases marked by deficiency of vital energy tumor cachexia group merges PDTC treatment group p < 0.05 compared with chronic diseases marked by deficiency of vital energy tumor cachexia group；* empty
Disease tumor cachexia merges PDTC treatment group p < 0.05 compared with chronic diseases marked by deficiency of vital energy tumor cachexia group；* chronic diseases marked by deficiency of vital energy tumor cachexia merges
PDTC treatment group p < 0.01 compared with chronic diseases marked by deficiency of vital energy tumor cachexia group).
Figure 10 is the mouse gastrocnemius weight and epididymal adipose tissues weight histogram of embodiment 2.A) chronic diseases marked by deficiency of vital energy tumour malignant disease in embodiment 2
The gastrocnemius that matter group and chronic diseases marked by deficiency of vital energy tumor cachexia merge PDTC treatment group is below blank control group again.B) the chronic diseases marked by deficiency of vital energy in embodiment 2
Tumor cachexia group epididymal adipose tissues are substantially less than blank control group again, and chronic diseases marked by deficiency of vital energy tumor cachexia merges PDTC treatment group and falls ill latter stage
Epididymal adipose tissues be significantly higher than chronic diseases marked by deficiency of vital energy tumor cachexia group again.(***p<0.001).
Figure 11 is the mouse spleen weight and index and spleen index histogram of embodiment 2.A) chronic diseases marked by deficiency of vital energy tumor cachexia closes in embodiment 2
And PDTC treatment group spleen is significantly higher than chronic diseases marked by deficiency of vital energy tumor cachexia group and blank control group again.B) chronic diseases marked by deficiency of vital energy tumour is disliked in embodiment 2
Sick matter group and chronic diseases marked by deficiency of vital energy tumor cachexia merge the index and spleen index of PDTC treatment group obviously higher than blank control group.(*p<0.05).
Figure 12 is the mouse thymus weight and thymus index histogram of embodiment 2.A) chronic diseases marked by deficiency of vital energy tumor cachexia group in embodiment 2
The chest gland weight for merging PDTC treatment group with chronic diseases marked by deficiency of vital energy tumor cachexia is substantially less than blank control group.B) chronic diseases marked by deficiency of vital energy tumor cachexia group
The thymus index for merging PDTC treatment group with chronic diseases marked by deficiency of vital energy tumor cachexia is substantially less than blank control group (p < 0.001 * * *).
Specific embodiment
The production side of the symptom binding model for the asthenic symptoms tumor cachexia that the present invention is further explained by the following examples
Method.Embodiment provided by the present invention can be successfully, reproduced chronic diseases marked by deficiency of vital energy tumor cachexia symptom combination animal model of the invention.
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..If not special indicate, embodiment
Used in the conventional means that are well known to those skilled in the art of technological means, raw materials used is commercial goods.
Do not make the biological experimental method illustrated in following embodiment, according to kit and product description into
Row.
The detection method for the various biological indicators that the present invention measures:
Capital equipment of the present invention:
Main agents of the present invention:
The foundation of 1 asthenic symptoms model of Preparative Example
Animal packet: 8 week old are bought from Shanghai western Poole-Bi Kai experimental animal company, the health hero that weight is 24 ± 2g
Property BALB/c mouse, is randomly divided into 2 groups: blank control group (8) and chronic diseases marked by deficiency of vital energy group (8).Blank control group is normally fed 26 days；
Chronic diseases marked by deficiency of vital energy group use bitter cold to rush down daily under, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy model, induce 26 days.
Under bitter cold is rushed down: the 1st~16 day, daily morning 8:00 stomach-filling cassia angustifolia leaf decoction 0.5mL, the 17th~26 day, it is daily on
Noon 8:00 stomach-filling cassia angustifolia leaf decoction 0.7mL；
Exhausted movemeat: starting to carry out mouse swimming power to exhaust daily at 1 point in afternoon, power exhaust standard be mouse show it is flurried, four
Even there is sinkage in limb exercise not harmony, and daily power exhausts 2 times, is spaced 10min；
Irregular diet: the next day fasting, free water, i.e. the 1st day morning, 8:00 put food, and late 8:00 removes food, fasting in second day；
Third day morning 8:00 puts food, and late 8:00 removes food, fasting in the 4th day, repeatedly.
Index observing includes: (1) weight: weighing in and records daily；(2) physiochemical indice: gastrin (GAS-17)；
(3) spleen weight and index and spleen index；(4) chest gland weight and thymus index.
Experimental result: research finds that three factor inducing mouse chronic diseases marked by deficiency of vital energy methods can cause animal to occur narrowing the apathetic existing of eye
As the symptom of the chronic diseases marked by deficiency of vital energy such as, diarrhea with loose stool, lazy move, chronic diseases marked by deficiency of vital energy group mouse shows weight hypothermia (as shown in Figure 1A, 1B)；Stomach is secreted
Cellulose content reduces (as shown in Figure 2)；Spleen weight and index and spleen index reduce (as shown in Fig. 3 A, 3B)；Chest gland weight and thymus index drop
Symptoms, chronic diseases marked by deficiency of vital energy models such as low (as shown in Fig. 4 A, 4B) induce successfully.
The foundation of 1 asthenic symptoms tumor cachexia model of embodiment etc.
Animal packet: 8 week old are bought from Shanghai western Poole-Bi Kai experimental animal company, the health hero that weight is 24 ± 2g
Property BALB/c mouse, be randomly divided into 4 groups: blank control group (8), chronic diseases marked by deficiency of vital energy group (8), tumor cachexia group (8), asthenic symptoms are swollen
Tumor cachexia group (8).
Blank control group is normal to feed 26 days；
Chronic diseases marked by deficiency of vital energy group, modeling pattern induce 26 days with the chronic diseases marked by deficiency of vital energy group in Preparative Example 1；
Tumor cachexia group, after normal nursing 10 days, after the right preceding oxter inoculation C26 colon cancer cell suspension of mouse again
Normal to feed 16 days, dosage of inoculation 0.1mL/ only, completed within 1 hour by seeded process；
Asthenic symptoms tumor cachexia group, modeling method include the following steps:
(1) under being rushed down using bitter cold, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, induction 10
It；
(2) C26 colon adenocarcinoma cell is inoculated with to the right preceding oxter of chronic diseases marked by deficiency of vital energy mouse, only, seeded process is 1 by dosage of inoculation 0.1mL/
It is completed in a hour；
(3) be inoculated with after simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 16 days；
Wherein,
Bitter cold rushes down lower revulsion: the 1st~16 day, whens daily morning 8, fed cassia angustifolia leaf decoction 0.5mL, and the 17th day~26 days
Cassia angustifolia leaf decoction 0.7mL is fed when the daily morning 8；
Irregular diet revulsion: the next day fasting, free water；
Exhausted movemeat revulsion: when daily afternoon 1, in 27-30 DEG C of water, weight bearing 5% swimming in tail portion is carried out to mouse and is instructed
Practice, forces mouse running to reach power and exhaust state；It is that mouse performance is flurried, major beat is uncoordinated or even occurs that power, which exhausts judgment criteria,
Sinkage, daily power exhaust 2 times, are spaced 10min；
Experimental result:
Research finds in entire experimental period that the weight and body temperature of blank control group are disliked obviously higher than chronic diseases marked by deficiency of vital energy group and the chronic diseases marked by deficiency of vital energy
Sick matter group (Fig. 5 A), illustrates that chronic diseases marked by deficiency of vital energy model is successful in entire experimental period.Chronic diseases marked by deficiency of vital energy cachexia group weight and body temperature are being tested
Later period is substantially less than chronic diseases marked by deficiency of vital energy group, has statistical difference (Fig. 5 B).In the cachexia later period, chronic diseases marked by deficiency of vital energy tumor cachexia and tumour are disliked
There is weight body temperature and is decreased obviously in sick matter, and shows that chronic diseases marked by deficiency of vital energy tumor cachexia can simulate two kinds of diseases of the chronic diseases marked by deficiency of vital energy and tumor cachexia
The symptom that crux is closed.Experiment mid-term has dead mouse, then 19 days by the next day fasting be changed to fasting on the half, chronic diseases marked by deficiency of vital energy group and the chronic diseases marked by deficiency of vital energy are disliked
Sick matter group weight and body temperature went up at experiment the 20th day, but were still below blank control group.
The study found that chronic diseases marked by deficiency of vital energy group gastrocnemius weight compares significant decrease with blank control group, there is statistical difference.The chronic diseases marked by deficiency of vital energy
Tumor cachexia group gastrocnemius is significantly lower than chronic diseases marked by deficiency of vital energy group and tumor cachexia group again, and statistical analysis has the anisotropic (figure of significance difference
6A).In terms of epididymal adipose tissues, chronic diseases marked by deficiency of vital energy group is substantially less than blank control group, and chronic diseases marked by deficiency of vital energy tumor cachexia group is disliked lower than chronic diseases marked by deficiency of vital energy group and tumour
Sick matter group (Fig. 6 B).Illustrate that chronic diseases marked by deficiency of vital energy tumor cachexia is better than simple tumour malignant disease to the degradation of gastrocnemius and epididymal adipose tissues
Matter.
The immune function of chronic diseases marked by deficiency of vital energy mouse can be substantially reduced, and spleen weight and index and spleen index and chest gland weight and thymus index are weighing apparatuses
Measure the key index of this function.For spleen, chronic diseases marked by deficiency of vital energy group spleen weight and index and spleen index are substantially less than blank control group；Tumour
The spleen weight and index and spleen index and blank control group of cachexia mouse are similar or slightly higher in blank control group；Chronic diseases marked by deficiency of vital energy tumor cachexia
The spleen weight and index and spleen index of mouse are similar with tumor cachexia group, are higher than chronic diseases marked by deficiency of vital energy group (Fig. 7).Its reason may be spleen conduct
The most important peripheral immune organ of body plays important filtering to exotic invasive bacterium, the tumour cell etc. in body and makees
With the compensatory of tumour stimulation spleen increases after inoculated tumour.For thymus gland, chronic diseases marked by deficiency of vital energy group chest gland weight and thymus index are significant low
In blank control group；The chest gland weight and thymus index of tumor cachexia mouse are substantially less than blank control group；Chronic diseases marked by deficiency of vital energy tumour is disliked
The chest gland weight and thymus index of sick matter mouse further decline under the collective effect that illness combines.Its thymus index is not only significant
Lower than blank control group, also substantially less than chronic diseases marked by deficiency of vital energy group (Fig. 8).
Above the experiment results show that chronic diseases marked by deficiency of vital energy tumor cachexia model can simulate the illness knot of the chronic diseases marked by deficiency of vital energy and tumor cachexia
Close feature.
Embodiment 2 uses the drug screening method of asthenic symptoms tumor cachexia model
Animal packet: 8 week old are bought from Shanghai western Poole-Bi Kai experimental animal company, the health hero that weight is 24 ± 2g
Property BALB/c mouse, is randomly divided into 3 groups: blank control group (8), asthenic symptoms tumor cachexia group (8), asthenic symptoms tumor cachexia
Merge drug (Tetramethylenedithiocarbamic acid, abbreviation PDTC) treatment group (8).
Blank control group is normal to feed 26 days；
Asthenic symptoms tumor cachexia group induces 26 days with the asthenic symptoms tumor cachexia group in embodiment 1；
Asthenic symptoms tumor cachexia merges PDTC treatment group, and modeling pattern is unique to distinguish referring to asthenic symptoms tumor cachexia group
It is to start within the 11st day intraperitoneal injection daily to give PDTC100mg/kg.
Experimental result: drug PDTC (100mg/kg) can inhibit decline of the chronic diseases marked by deficiency of vital energy tumor cachexia to weight and body temperature.
Such as Fig. 9-A, shown in B, the weight and body temperature of chronic diseases marked by deficiency of vital energy tumor cachexia group be substantially less than blank control group (pathological model modeling at
Function), and chronic diseases marked by deficiency of vital energy tumor cachexia merge PDTC treatment group weight body temperature be higher than chronic diseases marked by deficiency of vital energy tumor cachexia group, after the test the phase with
Chronic diseases marked by deficiency of vital energy tumor cachexia group is compared to there were significant differences.
Drug PDTC (100mg/kg) cannot alleviate degradation of the chronic diseases marked by deficiency of vital energy tumor cachexia to gastrocnemius.As shown in Figure 10 A, empty
The gastrocnemius of disease tumor cachexia group is substantially less than blank control group (pathological model modeling success), but chronic diseases marked by deficiency of vital energy tumor cachexia closes
And the weight body temperature of PDTC treatment group is similar to chronic diseases marked by deficiency of vital energy tumor cachexia group, is not significantly different.
Drug PDTC (100mg/kg) can alleviate degradation of the chronic diseases marked by deficiency of vital energy cachexia to epididymal adipose tissues.As shown in Figure 10 B, the chronic diseases marked by deficiency of vital energy
The epididymal adipose tissues weight of tumor cachexia group is substantially less than blank control group (pathological model modeling success), and chronic diseases marked by deficiency of vital energy tumour malignant disease
The epididymal adipose tissues weight that matter merges PDTC treatment group is significantly higher than chronic diseases marked by deficiency of vital energy tumor cachexia group.
Drug PDTC (100mg/kg) can increase spleen weight and index and spleen index, enhance body periphery immunity.Such as figure
Shown in 11A, 11B, the spleen that chronic diseases marked by deficiency of vital energy tumor cachexia merges PDTC treatment group is significantly higher than blank control group again；Chronic diseases marked by deficiency of vital energy tumour is disliked
The index and spleen index that sick matter merges PDTC treatment group is significantly higher than blank control group and chronic diseases marked by deficiency of vital energy cachexia group.
Drug PDTC (100mg/kg) cannot alleviate the reduction of chest gland weight and thymus index in chronic diseases marked by deficiency of vital energy cachexia, i.e., and PDTC pairs
Body central immune power does not influence.As shown in Figure 12 A, 12B, chronic diseases marked by deficiency of vital energy cachexia group and chronic diseases marked by deficiency of vital energy tumor cachexia merge PDTC and control
The thymic weight and thymus index for the treatment of group are substantially less than blank control group；Chronic diseases marked by deficiency of vital energy cachexia group and chronic diseases marked by deficiency of vital energy tumor cachexia merge
The thymic weight and thymus index of PDTC treatment group are not significantly different.
Above the experiment results show that the chronic diseases marked by deficiency of vital energy tumor cachexia model established can be used for investigating drug to chronic diseases marked by deficiency of vital energy malignant disease
The therapeutic effect of matter.Drug PDTC (100mg/kg) has certain therapeutic effect to chronic diseases marked by deficiency of vital energy tumor cachexia, can raise the chronic diseases marked by deficiency of vital energy
The weight of tumor cachexia animal, body temperature, epididymal adipose tissues weight, spleen tumor, index and spleen index, but chronic diseases marked by deficiency of vital energy tumour malignant disease cannot be influenced
The gastrocnemius weight of matter animal, thymic weight, thymus index etc..
Claims (10)
1. a kind of method for building up of asthenic symptoms tumor cachexia model, which comprises the steps of:
(1) under being rushed down simultaneously using bitter cold, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, induce 7-
15 days；
(2) to chronic diseases marked by deficiency of vital energy mouse inoculation C26 colon adenocarcinoma cell obtained in step (1), asthenic symptoms tumor cachexia model is obtained；
(3) be inoculated with after simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 15-18 days.
2. the method for building up of asthenic symptoms tumor cachexia model according to claim 1, it is characterised in that: bitter cold rushes down lower induction
Method are as follows: daily morning timing stomach-filling cassia angustifolia leaf decoction.
3. the method for building up of asthenic symptoms tumor cachexia model according to claim 1, it is characterised in that: irregular diet induction
Method are as follows: the next day feed, free water.
4. the method for building up of asthenic symptoms tumor cachexia model according to claim 1, it is characterised in that: exhausted movemeat induction
Method are as follows: daily timing in afternoon carries out running training or swimming instruction to mouse, forces mouse running to reach power and exhausts state.
5. the method for building up of asthenic symptoms tumor cachexia model according to claim 4, it is characterised in that: running training uses
The rotary-type tired instrument of mouse carries out；Reach power using running training and exhaust state, the power standard of exhausting is that tired instrument revolving speed is arranged in 30r/
Rest 15 times in min, mouse 30min, each time of having a rest in 30s or more, can be judged as that power exhausts state.
6. the method for building up of asthenic symptoms tumor cachexia model according to claim 4, it is characterised in that: use swimming instruction
Reach power and exhaust state, it is that mouse performance is flurried, major beat is uncoordinated or even sinkage occurs that power, which exhausts standard, and daily power exhausts 2
It is secondary, it is spaced 10min.
7. the method for building up of asthenic symptoms tumor cachexia model according to claim 1, it is characterised in that: in step (2)
Vaccination ways are that mouse oxter is inoculated with C26 colon adenocarcinoma cell, and C26 colon adenocarcinoma cell normal saline dilution to concentration is 1
×105-2×105A cell/mL, dosage of inoculation 0.1-0.2mL/ are only.
8. the method for building up of asthenic symptoms tumor cachexia model according to claim 1, which is characterized in that including walking as follows
It is rapid:
(1) under being rushed down using bitter cold, irregular diet, three factor revulsion of exhausted movemeat establish chronic diseases marked by deficiency of vital energy mouse model, induce 10 days；
(2) to chronic diseases marked by deficiency of vital energy mouse inoculation C26 colon adenocarcinoma cell；
(3) be inoculated with after simultaneously using bitter cold rush down under, two factor revulsion of irregular diet, continue induction 16 days；
Wherein,
Mouse uses BALB/c male mice, 8 week old, 24 ± 2g of weight；
Bitter cold rushes down lower revulsion: the 1st~16 day, whens daily morning 8, fed cassia angustifolia leaf decoction 0.5mL, and every 1g folium sennae crude drug mentions
Obtain 1mL cassia angustifolia leaf decoction, whens the 17th day~26 days daily morning 8 feeds cassia angustifolia leaf decoction 0.7mL；
Irregular diet revulsion: the next day fasting, free water；
Exhausted movemeat revulsion: when daily afternoon 1, in 27-30 DEG C of water, tail portion 5% swimming instruction of weight bearing is carried out to mouse, by force
Urgent mouse running reaches power and exhausts state；It is that mouse performance is flurried, major beat is uncoordinated or even sinks that power, which exhausts judgment criteria,
Phenomenon, daily power exhaust 2 times, are spaced 10min；
Vaccination ways in step (2) are that mouse oxter is inoculated with C26 colon adenocarcinoma cell, C26 colon adenocarcinoma cell physiology salt
It is 1 × 10 that water, which is diluted to concentration,5A cell/mL, dosage of inoculation 0.1mL/ are only.
9. the model established using the method for building up of asthenic symptoms tumor cachexia model according to claim 1 to 8
The method for screening the drug for treating chronic diseases marked by deficiency of vital energy tumor cachexia, this method comprises:
A) model is divided into blank control group, drug control group；
B) drug to be screened is administered to different drug control groups with therapeutically effective amount respectively, blank control group is not administered；
C) after an effective treatment cycle is administered, weight, the gastrocnemius weight, epididymal adipose tissues of the model in different groups are checked
The variation of heavy, spleen weight, chest gland weight or gastrin content's index refers to according to drug control group and blank control group at above-mentioned six
The significant statistical difference in more than one index in mark screens the drug for treating chronic diseases marked by deficiency of vital energy tumor cachexia.
10. the model that the method for building up of asthenic symptoms tumor cachexia model according to claim 1 to 8 is established exists
Screen the purposes in the drug for treatment chronic diseases marked by deficiency of vital energy tumor cachexia.
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