A Preliminary Study On The Relationship Between The Control Of Juvenile Gehua Hovenia Dulcis Thunb And The Prevention And Treatment Of Chronic Alcoholic Liver Injury In Rats

Background:Alcoholic liver disease is kind of liver damage caused by a large number of long-term intake of alcohol liver injury. With the increase of alcohol intake, the disease develops progressivily. from the initial development of alcoholic fatty liver for alcoholic-hepatitis, alcoholic liver fibrosis and alcoholic cirrhosis. With the improvement of modern living standard and the change of the diet, increased social intercourse, and the existence competition pressure increases, the trend of drinking and alcoholism is increasing. In Europe and the United States developed countries, it is at the top of cardiovascular disease, cancer accounts for the third of public health problems, after the main form is given priority to alcoholic fatty liver;In China, with China’s overall strength increasing, the incidence of alcohol disorders is growing, mainly composed of alcoholic hepatitis. In the treatment of alcoholic diseases at present, Comprehensive intervention of clinical general take alcohol and drugs, but patients with poor compliance, the curative effect of drug treatment has a lot of controversy. The doctor of traditional Chinese medicine since ancient times advocated not disease prevention first, both Hyman therapeutic principles, in terms of protecting liver therapy of traditional Chinese medicine also have congenital advantage, in the ancient literature, flower of kudzuvine hovenia dulcis thunb is one of the most representative drug therapy, Flower of kudzuvine function is activating spleen relieving alcoholism, Hovenia dulcis thunb has clear heat diuretic, the effect of drug therapy, The flower of kudzuvine and hovenia dulcis thumb, points away from top to bottom, the evil way, these the evil can spread from the table, but also from urine and solution, the role of bring out the best in each other,give the two drugs greatly enhance the efficacy of therapy. The early stage of the experimental group by using modern science and technology methods and means, observe the flower of kudzuvine hovenia dulcis thunb and different proportion compatibility (1,1,1,2, and 2:1), different extraction methods (water extraction and alcohol extraction) on rats with chronic alcoholic liver injury prevention and control research, the results show that the effect of the traditional water extraction is superior to the alcohol extraction, and the flower of kudzuvine hovenia dulcis thunb 2:1 ratio compatibility is the best solution to protect liver from damage.Objective:This experiment use the chronic alcoholic liver damage as the research object, from two angles of compatibility dosage and dosing cycle, discuss the amount of hovenia dulcis thunb flower of kudzuvine compatibility--effect relationship, clarify flower of kudzuvine hovenia dulcis thunb best compatibility conditions, hovenia dulcis thunb has flower of kudzuvine for clinical application reference for prevention and treatment of chronic alcoholic liver damage, to elucidate the mechanism of action of hovenia dulcis thunb flower of kudzuvine solution to protect liver.Method:Adaptability of rats fed a week later, according to the weight were randomly divided into 6 groups:blank group. model group, east treasure GanTai compatibility, low doses of compatibility, compatibility of dose and high dose. Adopt the method of 56°red star spirit erguotou lavage in rats with alcoholic liver damage model is established, in 4 weeks,8 weeks,12 weekends, randomly selected from each group 8 rats fasting water for 12 hours, 10% chloral hydrate anesthesia, abdominal aorta in blood. will be part of the whole blood into blank clean in vitro, part containing heparin sodium injection of clean in vitro, centrifugal separation of serum and plasma,-70° cryopreserved waiting for inspection. After taking blood, quickly cut the heavy first big leaves a piece of tissue of the liver/then put them in pathological stationary liquid, is used to observe histologic changes, then the rest of the liver tissue is divided into several small pieces, packing into the frozen pipe,-70°cryopreserved waiting for inspection.Content:The research content is divided into two aspects. (1) Hovenia dulcis thunb flower of kudzuvine compatibility of prevention and treatment of chronic alcoholic liver damage amount-research-effect relationship. Adopt the method of liquor lavage copy chronic alcoholic liver damage model, give the experimental animals of different doses and different medication treatment, by detecting blood alcohol concentration, alcohol dehydrogenase activity, liver index, serum liver function related indicators cereal third transaminase (ALT), aspertate aminotransferase (AST), total protein (TP), albumin (propagated), alkaline phosphatase (ALP) and liver pathological changes in the morphology observation of flower of kudzuvine hovenia dulcis thunb and compatibility of the prevention and control of chronic alcoholic liver damage amount--effect relationship. (2) Hovenia dulcis thunb flower of kudzuvine compatibility of chronic alcoholic liver injury rats "endotoxin-Kupffer cells-TNF alpha liver inflammation and liver cell apoptosis" way. Studies have shown that endotoxin and its activated hepatic Kupffer cells produce inflammation factor, which is the important mechanism of the alcoholic liver damage. Experiments in this paper by detecting "alcohol-endotoxin-Kupffer cells-TNF alpha liver inflammation and liver cell apoptosis" in the way of various cytokines (including endotoxin and TNF alpha, IL-1, IL-6 and INF-gamma, etc.) change and the change of liver cell apoptosis induced by alcohol, revealing the flower of kudzuvine hovenia dulcis thunb compatibility, toxin-liver inflammation-cell apoptosis mechanism of liver function.Result:① The effect of the compatibility of Gehua Hovenia on liver index of rats with alcoholic liver disease:flower of kudzuvine hovenia dulcis thunb compatibility of low dose group decreased liver index, the difference compared with model group;Hovenia dulcis thunb flower of kudzuvine dose group and high dose group in liver index decreased significantly over the weekend,12 difference compared with model group.② The effect of the compatibility of Gehua Hovenia on liver function of rats with alcoholic liver disease:Compared with model group,liver index of the low-dose group of Gehua Hovenia compatibility reduce at the end of 8th week and 12th week,and there was a significant difference compared with the model group. Liver index of middle dose group and high dose group reduced significantly at 12th weeks,compared with the model group.8th week and 12th week. In lowering blood ALT concentrations,model group was statistically different from the control group at the end of eight weeks. After 12 weeks of administration,TP in different compatible doses of Gehua Hovenia increased,only the low-dose group is statistically significant. After 12 weeks of administration,ALB in different compatible doses of Gehua Hovenia increased.with statistical difference.③ The effect of the compatibility of Gehua Hovenia on the alcohol density in serum and the activity of ethanol dehydrogenase(ADH)in liver with alcoholic liver disease:Compared with model group,at 8th week and 12th week of administration,blood alcohol concentrations of each dose compatible group were significantly lower than the model group, and until the end of the 12th week, compatible of low-dose group got the lowest blood alcohol concentration,with a statistically significant difference. At 8th week and 12th week of administration,the liver ADH activity of the low-dose group increased,with a statistically significant difference comparing with model group.④ The effect of the compatibility of Gehua Hovenia on Serum levels of ET-1.1, IL-6, IL-TNF alpha, INF-gamma in rats with alcoholic liver disease:Comprehensive analysis of the results of 4,8,12 weeks to see that flower of kudzuvine hovenia dulcis thunb 2:1 ratio compatibility including dose group in improving alcohol caused by endotoxin-Kupffer cells-TNF alpha-liver inflammation "way of various cytokines including endotoxin and TNF alpha, IL-1, IL-6, the INF-gamma has a certain trend, but the trend is not obvious improvement (compatibility in high dose group and low dose group slightly better), from the flower of kudzuvine hovenia dulcis thunb 2:1 ratio compatibility including dose group can be achieved through other ways to protect liver cell, alleviate the alcohol liver damage, it needs to be continued to discuss in the next experiment.⑤ The effect of the compatibility of Gehua Hovenia on Caspase-3 content in rats with alcoholic liver disease:At the end of 12 weeked,compared with the blank group rats,the liver caspase 3 levels of the high dose group reduced, combined with rat serum TNF alpha levels of inflammatory factors in the model group has a tendency to reduce, showed that high dose group of chronic alcoholic liver injury rat liver tissue caspase 3 activity has certain inhibitory effect.⑥ The effect of the compatibility of Gehua Hovenia on hepatic tissue pathologic of rats with alcoholic liver disease:In 8 and 12 weekend over the weekend, liquor lavage model group most animals appear inflammatory cells infiltration, fat cavitation and necrosis, alcoholic liver damage model copy success, flower of kudzuvine hovenia dulcis thunb compatibility of each dose group compared with model group rats in pathology have certain improvement effect.Compatibility of 12 weeks, low dose group and middle dose to improve compatibility of lesions was slightly better than the high dose group.Conclusions:①In terms of time, at 8th week and 12th week of administration,each compatible dose group showed a certain therapeutic effect,and improved the related indexes in varying degrees,especially directly reflected alcoholic liver injury indicators such as AST,ALT,ALP,TP,ALB and pathological aspects. The low-dose group is better than the high-dose group; At 8th week and 12th week of administration, In the metabolism of alcohol-related indicators such as ADH activity and blood alcohol concentration,the low-dose compatible group showed the best efficacy.②In alcoholic liver injury reaction mechanism of relevant indicators, the experiment of 4 weeks,8 weeks and 12 weeks, the flower of kudzuvine hovenia dulcis thunb compatibility in high dose group compared with blank group rats liver caspase 3 concentration is reduced, the caspase 3 activity has certain inhibitory effect, to improve the alcohol caused by endotoxin-Kupffer cells-TNF alpha-liver inflammation "way of various cytokines including endotoxin and TNF alpha, IL-1, IL-6, the INF-gamma has a certain trend, but the trend is not obvious improvement (compatibility in high dose group and low dose group slightly better), thus infer that flower of kudzuvine hovenia dulcis thunb 2:1 ratio compatibility of through other ways including dose group could protect liver cells, reduce liver damage caused by alcohol.