The Study Of Effects And Mechanism Of Polygonum Perfoliatum Lwith Hepatic Fibrosis Of Rats

Objective:Hepatic fibrosis is common pathological changes in chronic disease of liver,it is not only the development way of chronic liver disease to cirrhosis, but also throughout the development of liver cirrhosis, even developing to hepatocellalar carcinoma. Therefore the study of hepatic fibrosis has become a hot topic around our country and the world at present,and in order to block the occurring of cirrhosis and hepatocellalar carcinoma,to delay disease processing.Currently there is no specific medicine in treatment of hepatocellalar carcinoma. Recent research shows that Chinese medicine has great advantage in its treatment. This paper mainly makes a summarize which includes pathogenesis of hepatic fibrosis, composition of Perfoliatum perfoliatum L, and the relationship between Polygonum perfoliatum L and hepatic fibrosis.Quercetin and hyperoside are the active constituent of polygonum perfoliatum L. They have some function, such as removing free radicals, antioxidation, resistance to hepatitis b virus, inhibiting proliferation and activation of hepatic stellate cell(HSC), inhibiting collagen synthesis and protecting the liver.We have not seen the report of the therapeutic effect and mechanism of polygonum perfoliatum L in hepatic fibrosis(HF) of rats. We give rats dimethylnitrosamine(DMN)to establish hepatic fibrosis model, and then give different dose of polygonum perfoliatum L. morphological characteristics, weight, serum glutamic oxalacetic transaminase(AST), alanine aminotransferase(ALT), were observe.Serum hyaluronic acid(HA), laminin(LN) were measured by radioimmunoassay. The liver was histopathological analyzed for fibrosis by slice making and HE staining. And hepatic levels of transforming growth factor-beta1(TGF-β1), matrix metalloproteinase-1(MMP-1), matrix metalloproteinase-2(MMP-2), tissueinhibitor of matrix metalloproteinase-1(TIMP-1) were also measured by immunohistochemistry.And then we will discuss the function and mechanism of anti-inflammatory and anti-fibrosis of polygonum perfoliatum L.and providing scientific basis for clinical practice.Methods:Seventy-two SD rats of Level SPF,weight:180-220g, male, feed for adaptivelyfor2days,12rats per group, divide randomly into two groups: normal control group, positive control group, colchicin group, high dose polygonum perfoliatum L group, moderate dose group and low dose group.The research groups built a hepatic fibrosis model of the animal except normal control group. Model replication:2ml.kg-1for each rat,0.5%dimethyl nitrosamine (DMN) for intraperitoneal injection, continuous use for three days, drug discontinuance for four days, the time of model replication is4weeks, injection for12times in all.We use2/3dose in the first week, and the whole dose later. Drug manage:0.1mg.kg-1for colchicin group.7.5g.kg-1、5g.kg-1、2.5g.kg-1respectively for high dose polygonum perfoliatum L group, moderate dose group and low dose group. Normal control group and model group pour saline into stomach, other groups pour the same volume of drugs into stomach, ltime per day, continuous for4weeks. At the end of4th week, the experiment is over. All the rats have absolute diet and water for12hours. After weighing all of them, take blood for4-5ml from their eyes. AST and ALT were measured by Automatic biochemical analyzer (OLYMPUS-AU2700, Japan). HA and LN were measured by radioimmunoassay. The liver was histopathological analyzed for fibrosis by slice making and HE staining. And hepatic levels of TGF-β1, MMP-1, MMP-2, TIMP-1were also measured by immunohistochemistry.Result:The group of high and middle dose of polygonum perfoliatum L are better than the control group on the side of general form and weigh (p<0.05). High and middle dose of polygonum perfoliatum L reduced the content of serum AST, ALT, HA, LN, MMP-2, TIMP-1and TGF-p, level (P<0.05), but increase MMP-1level (p<0.05). In pathomorphology, High and middle dose of polygonum perfoliatum L suppressed the degree of hepatitis and fibrosis (p<0.05) in rat induced hepatic fibrosis.Conclusion:Polygonum perfoliatum L attenuates progression of hepatic fibrosis of rats induceded by dimethylnitrosamine. The mechanism is possibly as follow:1.Polygonum perfoliatum L improve general form and weigh of the rats of hepatic fibrosis, reduce serum AST、ALT、HA、LN. It indicated that polygonum perfoliatum L reduse hepatase and the index of cirrhosis, protecting liver, and suppress hepatic fibrosis. And it is related to the dose.2. In pathomorphology, polygonum perfoliatum L have the effect of anti-fibrosis.The mechanism is possibly related to alleviate degeneration and necrosis of the liver cells of hepatic fibrosis rats induceded by dimethylnitrosamine, reduce the activity of hepatitis, suppress the synthesis of collagenous fiber and reduse dysplasia of extracellular matrix(ECM). 3. Polygonum perfoliatum L reduce TGF-β1、TIMP-1、MMP-2level increase MMP-1, suppress proliferation and activation of HSC, reduce the synthesis of collagen, and increase degradation of ECM. degradation of Ⅰ,Ⅲ collagen.and increase degradation of ECM.In conclusion, polygonum perfoliatum L attenuates progression of hepatic fibrosis. The mechanism is muiti ways and target. Suppressing the expression of TGF-1is possibly one of the molecular mechanism of anti-hepatic fibrosis. The mechanism is possibly related to suppress the start of hepatic fibrosis through eliminating free redical, promoting antioxidation, reducing domino offect of cytokine, suppressing inflammation and apoptosis of hepatic cell.