中医,动物模型 z-bo 2020-07-27 622

    The animal models of TCM syndromes are "Yang Deficiency", "Yin Deficiency", "Spleen Deficiency", "Very Weak Pulse", "Blood Deficiency", "Congestion", "Liver Congestion", and "Cold Syndrome". And about "spleen deficiency". There are 11 types of "heat syndrome", "febrile illness" and "Leecy". In addition to some in vitro modeling ideas and methods, several pathogens similar to clinical syndromes are selected and acted on animals to generate models similar to specific clinical syndromes. Yes. .. The only pathogenic factor is physical factors. Chemical, biological, certain internal organs have been damaged or removed. ①Using rhubarb, senna leaves and Xuanmin powder to cause spleen deficiency and dysfunction model ②Using spleen deficiency to cause autonomic dysfunction, atropine (cholinergic M receptor blocker) drug), reserpine (a messenger of eating catecholamines) , Model of yang deficiency and yin deficiency; ③spleen and stomach damage, hunger and fullness according to the theory of pig fat in cabbage and traditional Chinese herbal medicine. It is used to cause eating disorders, spleen deficiency and biochemical waste models. A series of depletion phenomena reach depletion and compare yang-deficiency models. ⑤ Acute and fulminant E. coli sepsis can be replicated by intravenous injection of an appropriate dose of E. coli to compare febrile disease models. Inject highly toxic bacteria to "help the bad guys", ligate blood vessels to block blood supply, reduce the body's resistance to diseases, and create "apparent ways" for animal "apparent" models. In addition, various etiological modeling methods have been developed, and the animals used for modeling are mainly small animals (white mice, small mice), but there are also golden hamsters, rabbits and cats. In addition to gastric nutrition, the route of administration (or effect) is intramuscular, subcutaneous, intraperitoneal and ear vein injection. \r\nModeling method of animal model of TCM syndrome:\n 1. "Demenstration" model (Xiong Qida et al.: Sichuan Medicine, (2): 65, 1982): 2.1-2.75 kg rabbits are selected. Use 0.75 ml of highly toxic Escherichia coli (including 2.7 billion Escherichia coli/ml) per kilogram of body weight and inject it into the ear vein of the rabbit. After infection, the animals showed curling, laziness, lack of food, increased body temperature, rapid heart rate, bleeding from blood vessels in the ear cavity, bleeding, and obvious pathological changes in the tongue. Blood culture led to the growth of E. coli, showing significant reduction of white blood cells and platelets. The modeling is 100% successful and is suitable for studying experimental febrile diseases. \r\n 2. "Cold-heat syndrome" model (Liang Yuehua et al.: Medical Journal, (11), 1982): Choose female rats weighing 170-210g. Types of fever syndrome: use heat therapy drugs (aloe, dried ginger, cinnamon, codonopsis, astragalus, atractylodes, 100% decoction by oral tube). Types of cold syndrome: 1ml triple vaccine, first injected into the abdominal cavity twice a day, and then injected twice a day with 100 cold medicines (Dangkor, Coptis, Ferrodendron, Silverflower, Forsythia, Gypsum)% water decoction, 2 each time Milliliters can control the stomach. After 15 days of administration, the modeling success rate is 60-70%. Types of fever syndrome: increased heart rhythm, increased water consumption, increased urine output of catecholamines and 17-carboxycorticosteroids. Cold syndrome: decreased heart rate, decreased urine catecholamines, and excretion of 17-carboxycorticosteroids. You can use this model to measure pain threshold and cramp threshold as well as brain mediators. \r\n 3. "Congestion" model: high viscosity model (Ruan Jingchao, etc.): Choose a rabbit and inject 5 ml of 10% dextran salt solution per kilogram of body weight into the ear vein. This can be 100% successful. After administration, microcirculation blood slows down, red blood cells accumulate, whole blood and plasma viscosity increase, red blood cell sedimentation rate increases, and red blood cell electrophoresis slows down. This model is suitable for studying the mechanism of action of "blood activation and congestion" drugs. "Blood stasis" model (Mao Zemin: Beijing Medical Journal, (4): 305, 1981): Rats were selected and 0.1% adrenaline 0.2ml/dose was injected subcutaneously with ice water twice a day for 5 minutes. Except for stimulation. On the first or second day of administration, blood viscosity increased significantly, and on the second day after administration, blood fibrin and hematocrit levels also increased. This method is used for two consecutive days, killing every 48 hours, occasionally myocardial necrosis. Cardiomyopathy can simulate myocardial necrosis in Keshan disease. This model has been used to study the mechanism of high-dose vitamin C treatment of Keshan disease. "Blood stasis" model (Jin Huiming et al., Chinese Medical Journal, (1): 50, 1982.); rabbits were selected and 10% high molecular weight dextran (HMWD) saline was added at a dose of 1.5 g. It is injected into the ear vein at a dose of /kg. Thirty minutes after the injection, blood flow was observed from the microcirculation in the body, blood cells were strongly aggregated, blood cells were obviously scattered around the capillaries, and microvascular diseases and microcirculation diseases were observed. After 12 to 24 hours, the microcirculation disorder reaches its peak. This model is mainly used to study the principles of microcirculation diseases, herbal congestion, and blood circulation and stasis drugs. \r\nThe Second Military Medical University also adopted this method, using 2-2.5 kg body weight, 10% HMWD intravenous injection, 15 ml/kg female and male non-pregnant rabbits every week, to create one. It lasted ten weeks.\r\ nfour. "Blood deficiency" model (Ben Changen et al.: Journal of Traditional Chinese Medicine (6): 69, 1981): Male rats weighing 180-250 g were used. On days 1, 4 and 7 of the experiment, every 100 g of body weight 2% acetyl benzohydrazine (APH) is injected subcutaneously into saline, 1 ml is injected into 1 ml, and then 2 and 3 are injected for the second time. 0.5 ml. The formation of experimental hemolytic anemia. Red blood cells and hemoglobin are reduced, A large number of Heine bodies appear. It can last for 9-14 days. This model is suitable for blood and air deficiency research.\r\nFafu. "Spleen deficiency" model (Li Chuanying et al.: Xijiang Journal of Traditional Chinese Medicine (8): 355, 1982): Male rats were selected. Rhubarb, hot and sour powder, hot and sour powder soup, rhubarb, and senna injection were fed by tube feeding. After administration, the animals experienced diarrhea, weight loss, anorexia, mental atrophy and lack of luster. This is basically consistent with the clinical symptoms of patients with spleen deficiency. There are also reports about choosing Kunming male mice weighing 18-20 g, Wistar rats 70-100 g, and Syrian golden hamsters 25-70 g. The decoction is per Soak 0.5 g/ml/day/day into rhubarb water, weigh 0.7-1.25 g/ml 100 g golden hamster every day, 3-5 ml 15% rhubarb powder suspension. Feed the stomach once a day, every day Feed the mice twice, and successfully complete 90% or more sculptures 8 days after the administration.\r\n 6. "Reduced liver function" model (Chen Guolin): Choose small and small mice. Give the mouse peritoneum once a day Inject 0.6 ml of mugwort leaf injection (containing 0.3 g of crude drug) and sacrificed on the 45th and 60th day. Rats were injected intraperitoneally with 2 ml of mugwort leaf (containing 2.0 g of herbal medicine) once a day, half Replaced every other day after the month, and died 40 days later. Animals became depressed, attacked, bitten, ate less and gradually gained weight. Mice: Focal necrosis of the liver was observed in the 60-day group than the 45-day group Severe. Rat: Hepatocytes are swollen, cytoplasm is loose and granular, eosinophils infiltrate the portal vein, and the central vein is congested.\r\n 7. "Cancer deficiency" model: Choose male mice weighing 25-30 grams. About 7 times a day, about 7 successful high-dose hydrocortisone acetate intramuscular injections were successfully applied to study the effects of kidney drugs. In the subacute group, 5, 10, 20, 50, 100, 200 μg reserpine and 500 μg were used /kg (next afternoon) to treat acute tissue with reserpine. It will be administered. In the subacute group, 74μg/kg of actinomycin was administered intraperitoneally 7 times with 100% success. It is suitable for research on "cold limbs" "The etiology of the syndrome, and to study the mechanism of action of traditional Chinese medicine (Lizhong Decoction). Research. Can give mice 2.5 mg/day or 5-10 mg/day of methoxine, 95% of the models are completed normally in about a week. It is suitable for observing the relationship between receptor and thyroxine consumption. \r\n 8. "Yin deficiency" model: select male mice, weighing 20-30 g, thyroxine tablets 3 mg/mouse/month, reserpine 0.02 mg/mouse/day, press into powder, dilute with saline, shake well Feeding. management. The model was successfully used within 8 to 10 days and is suitable for studying the principles of genital nutrition. \r\n 9. "Yin syndrome" and "Yin syndrome" models (Dong Jun et al.: Shaanxi Journal of Traditional Chinese Medicine, (3): 1, 1981): Male mice weighing 20-30g were selected. Reserpine 10μg (dissolved in 0.1 ml normal saline)/mouse/day intramuscular injection, symptoms similar to Yin syndrome appear after 4-5 days; atropine 15-20μg/mouse/day intramuscular injection and Yin syndrome appears after 2 days Signs of similar symptoms. It is suitable for observing the functional changes of various organ systems of the human body, the electrophysiological changes at the cellular level, and the changes caused by the aforementioned Campo and acupuncture treatments. \r\nTen. The model of "impulse dysfunction" (Zuo Zhen et al.: Journal of the Second Military Medical University (1): 1982 No. 19): Choose a cat with a 3% sodium pentobarbital solution at a dose of 0.25 to 0.5 ml/kg. I will. Take the femoral vein as a model. After the injection, the myocardial contractility decreased significantly, and the blood pressure dropped to about 10 mmHg. The animal's femoral artery pulsated faintly with little contact. Fits 100% shape. It is suitable for observing aconitum specimens and heart enhancers. Acute effects of isolates. \r\n 11. "Insufficient blowing" model (Shanghai Second Medical University: Shanghai Journal of Traditional Chinese Medicine (5): 1964 No. 8): Rabbits weighing 1.07 to 2.5 kg are modeled by artificial chronic anemia . .. Take about 10 ml of blood from the ear artery, ear vein or heart every day. Animals suffer from mental atrophy, lethargy, curled limbs, muscle weakness and temperatures just above normal body temperature. Hematocrit decreased, total protein decreased slightly, tongue pale, fat, soft and moist. Suitable for learning the "mentally handicapped" tongue. \r\n 12. "Yin-yang imbalance" model (Yang Lianqing et al.: Journal of Integrated Traditional Chinese and Western Medicine (6): 353, 1983): Choose male Wistar rats weighing 235-297 g. In the afternoon (7-day experiment), 7 exogenous glucocorticoid dexamethasone suspension 7.5μg/100g body weight test tube was administered to the algae stomach. The other group received 28 tubes of nutrition in the same way. Number of days (30 days for the experiment). Electron microscopy showed mitochondrial degeneration of adrenal cyst-like ribbon cells in animals, low plasma corticosterone levels, and inhibition of HPA (hypothalamic-pituitary-adrenal cortex) axis function. I. \r\n 13. "Start" mode (such as Sun Aizhen): Choose a dog based on the theory of "war between good and evil" in herbal medicine. "Helping the evil" refers to selecting highly toxic bacteria that have been repeatedly cultivated to increase their ability to cause viruses and injecting these bacteria into the muscle layer of the appendix. "Injury": There is a hole in the root of the appendix, which can block blood circulation and significantly weaken the body's resistance to diseases. Within 2 days after the operation, refusal to eat, atrophy, fatigue and immobility; macroscopic specimens show enlarged appendix, vasodilatation, hyperemia, purulent and fibrous exudate on the serous membrane surface, thickening of the intestine, edema and diffuse mucosa with ulcers Necrosis, concentrated exudate in the cavity, microscopic examination: purulent exudate in the appendix cavity, mucosal necrosis, shedding, granulation tissue hyperplasia, hyperemia, edema, white blood cells, and increased MPT. It is suitable for studying the analgesic principle of TCM Tongli and the pharmacological effects of Dachengqi Decoction and other compounds. \r\nThe animal models of TCM syndrome include: Yang deficiency, Yin deficiency, spleen deficiency, weak pulse, blood deficiency, blood stasis, liver depression, and "cold syndrome" and "spleen deficiency". There are 11 types of "heat syndrome", "febrile illness" and "Leecy". Except for a few in vitro, the idea and method of modeling is to select some pathogenic factors that are similar to clinical syndromes and act on the animal body to generate models similar to specific clinical syndromes. .. The causative factors are only physical. Chemical, biological and specific internal organs are damaged or removed. ①Using raw rhubarb, senna leaves and Xuanmin powder to cause spleen deficiency and dysfunction model ②Atropine (cholinergic M receptor blocker), reserpine (catecholamine transmitter consumption) using spleen deficiency that causes autonomic dysfunction, The model of yang deficiency and yin deficiency; ③According to the theory of spleen and stomach damage, cabbage and pig fat in traditional Chinese medicine according to hunger and fullness. Used to cause eating disorders and spleen deficiency and biochemical exhaustion models. A series of depletion phenomena reach depletion and compare yang-deficiency models. ⑤ Acute and fulminant E. coli sepsis can be replicated by intravenous injection of an appropriate amount of Escherichia coli to compare febrile disease models. Inject highly toxic bacteria to "help the evil", ligate blood vessels to cut off the blood supply, reduce the body's resistance to diseases, and create one in the "seeming" model of animals to "break the right way". In addition, a variety of etiological modeling methods have been developed. The animals used for modeling are mainly small animals (white and small mice), but there are also golden hamsters, rabbits and cats. In addition to gastric nutrition, the route of administration (or effect) is intramuscular, subcutaneous, intraperitoneal and ear vein injection.

　　Modeling method of animal model of TCM syndrome:

　　1. Model of "Blood in Go Period" (Xiong Qida et al.: Sichuan Medical Journal, (2): 65, 1982): Choose rabbits weighing between 2.1 and 2.75 kg. Use 0.75 ml of highly toxic Escherichia coli (containing 2.7 billion Escherichia coli/ml)/kg body weight to inject into the ear vein of the rabbit. After infection, the animals showed curling, laziness, lack of food, increased body temperature, increased heart rhythm, bleeding around the blood vessels in the ears, hemorrhage, tongue showed obvious pathological changes, blood culture results showed the growth of E. coli, white blood cells and platelets decreased significantly . The modeling is 100% successful, and it is suitable for studying experimental fever diseases.

　　2. Model of "cold syndrome and fever syndrome" (Liang Yuehua et al.: In Medical Journal, (11), 1982,): Female rats weighing 170-210g were selected. Fever syndrome type: use hyperthermia drugs (aloe, dried ginger, cinnamon, codonopsis, astragalus, atractylodes macrocephala), and 100% decoction by oral tube. Types of cold syndrome: 1ml triple vaccine, first injected into the abdominal cavity twice a day, and then 100% water decoction made of cold medicines (dancol, coptis, ferrodendron, silver flower, forsythia, plaster) twice a day, 2 ml each time, manage the stomach. After 15 days of administration, 60-70% modeling was successfully performed. Types of fever syndrome: increased heart rhythm, increased water consumption, increased urine output of catecholamines and 17-carboxycorticosteroids. Cold syndrome: decreased heart rate, decreased urine catecholamines, and excretion of 17-carboxycorticosteroids. This model can be used to measure pain threshold and cramp threshold as well as brain media.

　　3. "Congestion" model: high viscosity model (Ruan Jingchao, etc.): select rabbits and inject 10% dextran saline into the ear vein, 5 ml per kilogram of body weight. This can be 100% successful. After administration, microcirculation blood slows down, red blood cells accumulate, whole blood and plasma viscosity increase, red blood cell sedimentation rate increases, and red blood cell electrophoresis slows down. This model is suitable for studying the mechanism of action of "blood activation and decongestion" drugs. "Blood stasis" model (Mao Tengmin: Beijing Medical Journal, (4): 305, 1981,): select rats, subcutaneously inject 0.1% adrenaline 0.2ml/dose twice a day, and add ice water for 5 minutes to stimulate. On the first or second day of administration, blood viscosity increased significantly, and on the second day after administration, fibrin and hematocrit in the blood also increased. This method was used for two consecutive days, killing once every 48 hours, and occasional necrosis in the myocardium appeared. Cardiomyopathy can simulate myocardial necrosis in Keshan disease. This model has been used to study the mechanism of high-dose vitamin C treatment of Keshan disease. "Blood stasis" model (Jin Huiming et al., Chinese Medical Journal, (1): 50, 1982.); rabbits were selected and 10% high molecular weight dextran (HMWD) saline was added at a dose of 1.5 g. It is injected into the ear vein at a dose of / kg. Thirty minutes after injection, blood flow can be observed from the microcirculation in the body, blood cells violently aggregate, blood cells are clearly scattered around the capillaries, and microvascular and microcirculation disorders are observed. After 12 to 24 hours, the microcirculation disorder reaches its peak. This model is mainly used to study microcirculation system diseases, herbal stasis, and the principles of blood circulation and stasis drugs.

　　 The Second Military Medical University also uses this method, using male and female non-pregnant rabbits weighing 2-2.5 kg, 10% HMWD intravenous injection, 15 ml/kg each time, twice a week, creating a “congestion model”. It lasted ten weeks.

　　4. "Blood deficiency" model (Ben Changen et al.: Journal of Traditional Chinese Medicine (6): 69, 1981,): Male rats weighing 180-250 g were used. On day 1, 4 and 7 of the experiment, 2% acetyl benzohydrazine (APH) per 100 g of body weight was subcutaneously injected into saline, 1 ml was injected at 1 ml, and 2 and 3 were injected at the third. It is 0.5 ml. The formation of experimental hemolytic anemia. Red blood cells and hemoglobin are reduced, and a large number of Heine bodies appear. It can last for 9-14 days. This model is suitable for studying blood deficiency and qi deficiency.

　　 5. "Spleen deficiency" model (Li Chuanying et al.: Xijiang Journal of Traditional Chinese Medicine (8): 355, 1982): Male rats were selected. Rhubarb, hot and sour powder, hot and sour powder soup, rhubarb and senna injection are administered by tube feeding. After the administration, the animals developed diarrhea, weight loss, loss of appetite, mental atrophy and lack of luster, which were basically consistent with the clinical manifestations of patients with spleen deficiency. There are also reports on selecting Kunming male mice weighing 18 to 20 g, Wistar rats weighing 70 to 100 g and Syrian golden hamsters weighing 25 to 70 g. The decoction was immersed in rhubarb water, 0.5 g/ml/day/each time, with 100 g Golden Hamster weighing 0.7-1.25 g/ml, 15% rhubarb powder suspension 3-5 ml every day. The stomach was fed once a day, and the mice were fed twice a day, and 90% or more of the sculpture was successfully completed on the 8th day after the administration.

　　6. "Reduce liver function" model (Chen Guolin): Choose large and small mice. The mice were intraperitoneally injected with 0.6 ml of wormwood leaf injection (containing 0.3 g of crude drug) once a day, and they were sacrificed on 45 and 60 days respectively. Rats were injected intraperitoneally with 2 ml mugwort leaf injection (containing 2.0 g crude drug) once a day, replaced every other day after half a month, and died 40 days later. Animals will be irritated, attacked, bitten, eat less and gradually gain weight. Mice: The liver has focal necrosis, and the 60-day group is more severe than the 45-day group. Rat: Hepatocytes are swollen, cytoplasm is loose and granular, eosinophils infiltrate the portal vein, and the central vein is congested.

　　7. "Gan's Deficiency" model: Male mice weighing 25 to 30 grams are selected. Once a day, about 7 times, about 7 successful intramuscular injections of high-dose hydrocortisone acetate, suitable for studying the effects of kidney drugs. 20-28g mice can also be used. In the subacute group, 5, 10, 20, 50, 100, 200 μg reserpine and 500 μg/kg (the following afternoon) are used to treat the acute tissues of reserpine. Be managed. In the subacute group, 74 μg/kg of actinomycin was added 7 times and administered intraperitoneally, but all were 100% successful. It is suitable for studying the cause of "cold limb" syndrome and exploring the mechanism of action of traditional Chinese medicine (Lizhong Decoction). the study. Mice can be fed 2.5 mg or 5-10 mg/day of methoxine per day, and 95% of the modeling is successfully completed in about a week. It is suitable for observing the relationship between receptors and thyroxine consumption.

  8. "Yin deficiency" model: select male mice, weighing 20-30g, thyroxine tablets 3mg/mouse/month, reserpine 0.02mg/mouse/day, pressed into powder, diluted with saline, shaken and tubed feed. management. The model is successful in 8 to 10 days and is suitable for studying the principles of genital nutrition.

  9. "Yin syndrome" and "Yang syndrome" models (Dong Jun et al.: Shaanxi Journal of Traditional Chinese Medicine, (3): 1, 1981): Male mice weighing 20-30g were selected. Reserpine 10μg (dissolved in 0.1 ml saline)/mouse/day intramuscular injection, symptoms similar to Yin syndrome appear after 4-5 days; Atropine 15-20μg/mouse/day intramuscular injection and Yin syndrome appear after 2 days Similar symptoms. It is suitable for observing the functional changes of the various organ systems of the human body, the electrophysiological changes at the cell level, and the improvement of the above changes by Chinese medicine and acupuncture.

　　10. The model of "pulse dysfunction" (Zuo Zhen et al.: Journal of the Second Military Medical University (1): 19, 1982): select cats with a dose of 0.25 to 0.5 ml/kg of 3% pentobarbital sodium solution. Take the femoral vein as a model. After the injection, the myocardial contractility was greatly weakened, and the blood pressure dropped to about 10 mmHg. The animal’s femoral artery pulsated faintly and was barely touchable. Fits 100% shape. It is suitable for observing aconitum preparations and heart enhancers. Acute effects of isolates.

　　11. "Qi Deficiency" model (Shanghai Second Medical University: Shanghai Journal of Traditional Chinese Medicine (5): 1964 No. 8): Rabbits weighing 1.07-2.5 kg are modeled by artificial chronic anemia. About 10 ml of blood is drawn from the ear artery, ear vein or heart every day. Animals may suffer from mental atrophy, lethargy, curled limbs, muscle weakness and slightly higher than normal body temperature. Hematocrit is reduced, total protein is slightly lower, and tongue is pale, fat, soft and moist. Suitable for learning the "mentally lacking" tongue.

　　12. "Yin and Yang imbalance" model (Yang Lianqing et al.: Journal of Integrated Traditional Chinese and Western Medicine (6): 353, 1983): Choose male Wistar rats, weighing 235-297g. The exogenous glucocorticoid dexamethasone suspension 7.5μg/100 g body weight tube was administered 7 times in the stomach of the algae every afternoon (7 days of experiment). The other groups were given 28 tube feedings in the same way. I took a rest 2 Days (30 days for the experiment). Electron microscopy showed mitochondrial degeneration of adrenal cyst-like ribbon cells in animals, low plasma corticosterone levels, and inhibition of HPA (hypothalamic-pituitary-adrenal cortex) axis function. I'm.

　　 13. "Departure" mode (Sun Aizhen, etc.): Choose dogs based on the theory of "fighting good and evil" in Chinese medicine. "Helping evil" refers to selecting highly toxic bacteria that have been repeatedly cultivated to increase their ability to cause viruses. These bacteria will be injected into the muscle layer of the appendix. "Injury": piercing the root of the appendix, blocking blood circulation, significantly weakening the body's ability to resist diseases. Within 2 days after the operation, refusal to eat, atrophy, tiredness and inability to move; macroscopic specimens showed enlarged appendix, vasodilation, hyperemia, purulent and fibrous exudate on the serous membrane surface, thickening of the intestine, edema and diffuse mucosal necrosis And ulcers, concentrated exudate in the cavity, microscopic examination: purulent exudate in the appendix cavity, mucosal necrosis, shedding, granulation tissue hyperplasia, hyperemia, edema, white blood cells, MPT surge. It is suitable for studying the principle of pain relief by TCM Tongli and the pharmacological effects of Dachengqi Decoction and other compounds.