The Application And Basic Research With Jia Wei Wei Ling Decoction In The Treatment Of Ascites Due To Cirrhosis

Objective: Ascites due to cirrhosis is one of the clinical common diseases and difficult to cure, which belongs to "accumulation", "hypochondriac pain", "tympanites" in TCM, clinically in modern medicine support treatments are mainly used, butthe curative effect is common. Jiawei Weiling decoction is professor menjiuzhang’s effective empirical foumula according to liver disease characteristics and clinical practice for the treatment of ascites due to cirrhosis.This project mainly through clinical observation and animal experiment is to further verify the effect of Jiawei Weiling decoction, and also provide relative experimental data about the effectiveness and scientificalness in treatment of cirrhosis with ascites, and provide a useful reference for the clinical treatment of cirrhosis ascite.Methods:This study includes experimental research,clinical research. In the first part, the rat model of liver cirrhosis with ascites was established by using two methyl nitrite(DMN). 100 adult male SD rats whose weight was 200g~250g fed with, 10 rats were selected as normal control group, the remaining 90 as cirrhosis model group. Familiar with the environment a week after, each to dimethylnitrosamine in rats by intraperitoneal injection of 1%(DMN)by the dose of 1ml / kg body weight, three days a week, once a day,for a total of 12 weeks, pay attention to if rats weight is before a decline in more than 30%, stop the intraperitoneal injection until the body weight recovery to more than 200. Every twelfth weeks to measure, to determine whether the ascites puncture. Randomly selected eight abdominal puncture ascites in rats and eight normal control group rats were dissected, naked eye observation of liver and spleen of morphological changes, The portal vein pressure was measured by cather insertion method, liver specimens were obtained for pathological studies, blood samples were obtained for liver and kidney function test. The second part in the first part of the successful model based and other drugs compared to observe the therapeutic effect of Jia Wei Weiling Decoction on cirrhotic rats with ascites model therapeutic effect and mechanism research.The decompensated cirrhotic rat model complicated with ascites were randomly divided into five groups:Jiawei Weiling Decoction high dose group(group A)and Jiawei Weiling Decoction low dose group(group B), model group(Group C), furosemide and spironolactone group(Group D), Fuzheng Huayu group(group E), each had 8 rats.At first,gathered urine and recorded the total net fluid-excretion volume,then according to their grouping,Group A,B were given Jiawei Weiling Decoction respectively in the dose of42.7g/kg body weight(BW),6.1g/kg(BW). Group D was given furosemide and spironolactone 0.66mg/kg BW,group E was given Fuzheng-Huayu capsule 0.075g/kg BW. The rats of normal group and model group were given equivalent normal saline by gavage once per day for 3 weeks.The general situations of rats were observed during the experiment.during the experiment. The five groups were all administered for3 weeks, After gathering urine and recording the total 24-hour netfluis-excretion volume again in the 3 weeks,we killed all the rats and the portal vein pressurw was measures by catherer insereion method and observed the appearance and pathological changes of their livers with HE staining.the blood samples were obtained fou the serum parameters of liver function and the content of No and ET-1.ALT, AST, and TIBL and ALB were determined by automatic biochemical analyzer; serum markers of hepatic fibrosis HA, LN, PC III and CIV were detected by radioimmunoassay; The third part of the clinical curative effect observation of Jia Wei Weiling Decoction in the treatment of cirrhosis. a total of 60 cases were randomly divided into the treatment group and the control group.30 patients in treatment group were treated by the traditional Chinese medicine of Jiawei Weiling Decoction,combining with routine Western medicine;30 patients in control group were treated symptomatic treatment with routine Western medicine. The period of treatment is one month.observed the changes of symptoms and signs、liver function 、body weight、abdominal circumference、abdominal ultrasonography before and after the treatment and the complication situation and monitored the 24 h amount of urine.observed the general medical examination for the body(for example T,P,R,Bp),blood and urine routine test,stool routine test and kidney function,the electrocardiogram and untoward effect.Results :1 After 12 weeks, 51 rats survived in which 48 rats had ascites.The pathological study showed the formation of liver cirrhosis.Splennomegaly was also present.The portal vein pressure cirrhosis model group was obviously higher than normal control group(p<0.01). Ascites due to cirrhosis group, The levels of serumtotal bilirubin(TB), alanine aminotransferase(ALT), aspartate Transaminase(AST) were higher than normal control group(P<0.01).while the level of serum albumin was lower in cirrhotic rats(P<0.05).2 The general conditions of health of the rats:It is observed that tangled and bloom fur,descent of activity amount,decrease of drink and food,loss of weight,loose feces occurred in the model group rats with ascites in cirrhosis. After the start of treatment group, all of the changes mentioned above were improved.Among them,group A and group B than that of other groups is the most significant change after treatment by dilute stool semiliquid stool during making the model into the normal stool.2.1 After the experiment, there was a small amount of ascites in group A and group B and much ascites in group C.there was no ascites in group D.Compared with group C, the differences were significant(P<0.05),which was correspongdent to group E.2.2 By comparing the volume of post-therapy with one of pre-therapy,group A,B and D could signigicantly increase the 24-hour net excretion volume(P<0.01).But there were no signigicant changes in group E(P>0.05).2.3 Portal venous pressure of the rats of group A ob-viously lower Portal venous pressure of the rats of group C,Compared to model group,the difference was significant(P<0.01).Pressure from other therapeutic groups(group B,D,E) droped too,but the differences compared to group C were not obvious such as group A(p<0.05).2.4 Jiawei Weiling Decoction could obviously relieve the inflammation of the liver tissues and the hyperplasia of collagen fibers.The effect was equal compared to group E(p>0.05).2.5 The contents of indexes of hepatic function in Model group(Group C) rats including ALT、AST and GLB were significantly increased,but the level of ALB decreased;After the treatment in Jiawei Weiling Decoction(group A)and Fuzheng Huayu capsule(group E)the contents of ALT、AST and GLB decreased obviously,and the contents of ALB increased.Compared with group C,there were significant differences.2.6 The contents of NO and ET-1 in group C were higher than those of group F.After the treatment,in all groups,the contents of NO and ET-1 decreased.The contents of group A changed obviously(compared to group C p<0.05).2.7 The contents of HA、LN、PCⅢ and CIV in group C increased obviously. After the treatment,they decreased in the other groups.But the contents of HA、LN、PCⅢ and CIV in group D did not change(compared to group C p>0.05).3 The comparison of general therapeutic effect and clinical symptom:the total efficiency of therapeutic group(93.33%) was significantly different from that of the control group(70%);the improvement of clinical symptom in two groups had significant difference(P<0.05).3.1 The improvement of the main symptoms and signs in the two groups before and after the treatment, therapeutic group is obvious in the improvement of main symptoms and signs after treatment(P<0.05);after treatment of patients in the control group the main symptoms and signs also improved, but the improvement in control group was lower(P>0.05).3.2 Comparison of indexes of liver function and PTA before and after treatment, the levels of ALB and PTA, A/G increased significantlyin therapeutic group(P<0.05). the levels of ALB, PTA, A/Glevel in the control group also increased,but the difference was not significant(P>0.05); the levels 0f AST, ALT, TBIL of the two groups decreased slightly after treatment(P>0.05), the levels of ALB and PTA,A/G between the two groups after treatment was significant(P<0.05).3.3 Weight, abdominal circumference and the average 24 h urine amount comparison before and after the treatment,the difference of weight, abdominal circumference and the average 24 h urine amount between the two groups were significant(P<0.05); the difference of weight and abdominal circumference were not sinificant(P>0.05),but the average 24 h urine amount in the control group before and after treatment was changed significantly(P<0.05).3.4 Ultrasonograph comparison two before and after the treatment.there was improvement in the thickness of spleen, inside diameter of portal vein and splenic vein portal vein and spleen vein width between the two groups after the treatment, but the difference was not significant(P>0.05); the thickness of spleen,inside diameter of portal vein and splenic vein portal vein and spleen vein width in each group changed obviously before and after the treatment(P<0.05).3.5 Integral calculus of ascetic capacity in both groups after the treatment all decreased.In the therapeutic group the difference before and after the treatment was significant(P<0.05),but in the control group before and after the treatment the difference does not have significance(P>0.05); the difference between the two groups after the treatment was significant. difference indicating the regression of ascites in therapeutic group was greater than thatin control group.3.6 The incidence of complications in the two groups were 13.33%and 23.33%, respectively, and there was no significant difference in the incidence of complications(P>0.05).3.7 The patients of the two groups before and after the treatment in blood, urine, stool routine, general physical examination,kidney function, electrocardiogram index had no obvious abnormal changes; Jia Wei Weiling Decoction in treating ascites due to cirrhosis have no obvious toxic and side effects.Conclusions:1 A decompensated cirrhotic rat model complicated with ascites was successfully established.2 Jiawei Weiling decoction can significantly change mental state of model rat, skin luster, and promote appetite, and increases weight and significantly reduce the amount of ascites in rats.3 Jiawei Weiling decoction could signigicantly increase the 24-hour net excretion volume(p<0.01).4 Jiawei Weiling decoction could lower portal venous pressure of the model rats.5 Jiawei Weiling decoction could significantly reduce inflammation of liver tissue and inhibit the hyperplasia of collagen fiber,exhibited hepatoprotective and antifibrotic effects better.6 Jiawei Weiling decoction could lower the contents of NO and ET-1.This could be the one of mechanisms which Jiawei Weiling decoction resists portal hypertension.7 Treatment group using Jiawei Weiling Decoction in the treatment of liver cirrhosis with ascites certainly, in improving symptoms and signs, liver function is better than the control group, andreduce the complications occurred, to reduce the pain of patients,improved the quality of life of patients, and no adverse reaction,for the treatment of ascites due to cirrhosis provides a very good idea.8 Jiawei Weiling decoction combined with symptomatic treatment of Western medicine of traditional Chinese medicine and Western medicine combination group in improving the efficacy, alleviate the patient’s clinical symptoms, improve the liver function is superior to simple western medicine symptomatic treatment group; it can improve the clinical symptoms of the patients, but also can improve the liver function of patients with: AST, ALT, ALB, TB, and PTA;it can stabilize the plasma albumin level, improve the function of blood coagulation, reduce the economic pressure of patients,reduce bleeding and other complications;it can gain better long-term clinical curative effect to the patient.