The Study Of Sinisan Jiawei On TGF-β1and Rhoa Related Signal’s Regulation In Rat Liver Tissue Of Hepatic Fibrosis

Purpose and significance of studyHepatic fibrosis is a common pathological basis of many chronic liver diseases, early stage cirrhosis of the liver is reversible, cirrhosis can not develop liver cirrhosis stage if it is intervened timely, otherwise it may progress to cirrhosis, liver cirrhosis is hard to reverse. Therefore, it’s significant for preventing the further development of chronic liver disease to explore the pathogenesis of liver fibrosis and develop some effective drugs for liver fibrosis, and it has an important clinical value for reversing the early hepatic fibrosis. In recent years, our traditional Chinese medicine has shown a relatively bright development prospects in the study on prevention and cure of liver fibrosis. And it’s reported that a large number of traditional Chinese medicine preparations have the effect of anti-liver fibrosis. But many of the studies on the Chinese native medicine preparation are confined to preliminary clinical observation and animal experiment, and lack in the system research about molecular mechanism of action, the situation is not conducive to the needs of the development of modernization of Chinese medicine. So we need the further researches badly and explore more safe and effective compound Chinese medicine anti-liver fibrosis. Our previous clinical observation,"according to liver fibrosis with liver qi stagnation, spleen deficiency of Collaterals Disease machine has the characteristic of, Sinisan Jiawei prescription treatment in120cases of liver fibrosis, confirmed four inverse scattered prescription can significantly improve liver function, reduce the indexes of liver fibrosis, improve the liver tissue structure of the obvious anti-fibrosis effect. But the precise molecular mechanism is still not clear, and at present there few reports for its further study domestic and overseas. Therefore, it is necessary to study deeply the mechanism of occurrence and development of liver fibrosis, and the mechanism of treating liver fibrosis about Sinisan Jiawei flavored, four inverse scattered compatibility. Sinisan Jiawei is a basic prescription in clinical liver qi, it has the good efficacy of Shugan Jieyu, but it also has its shortcomings. Mang years’clinical experience in treating proves that the treatment effect of using Sinisan Jiawei is better than Sinisan. In the clinical and experimental research derived from Sinisan Jiawei Decoction on liver fibrosis has exact efficacy, and based on the theory of the liver controlling dispersion, this study study deeply the mechanism of Sinisan Jiawei disassembled prescription and prescription of anti-liver fibrosis. Observing the effects of different doses of Sinisan Jiawei, the influence of Sinisan’s compatibility formula on the immune damage and hepatic fibrosis in rats model, and exploring the Sinisan compatibility and its molecular mechanism of liver fibrosis resistant, provide experimental basis for clinical application and development of new drugsThe method of studyThis paper is divided into two parts, theoretical study and experimental study. The part of theory research combining the system basis of traditional Chinese medicine on hepatic fibrosis of understanding of ancient and modern literature with modern medicine research progress of hepatic fibrosis, focus on the traditional Chinese medicine etiology and pathogenesis of liver fibrosis, liver fibrosis treatment of traditional Chinese medicine research status, the immunological pathogenesis of liver fibrosis, the thought of Sinisan jiawei compatibility prescription, and all these provide the theory basis for the Sinisan Jiawei modified against liver fibrosis.Experimental research part, first of all, using pig serum induced immune damage liver fibrosis model, and using light microscopy and immunoblotting, RT-PCR, immunohistochemistry and molecular biology techniques and so on monitored the effectiveness of Sinisan, Sinisan Jiawei on liver fibrosis. Sinisan jiawei on TGF-β1and RhoA related signal’s regulation in rat liver tissue of hepatic fibrosis provides experimental basis for clinical application and development of new medicines and f Sinisan powder prescription.The conclusion and significance of studyThis topic regarding the liver controlling dispersion theory as a guide, and using Sinisan Jiawei on treatment of liver fibrosis rat model get the following conclusions:1. The theory of liver controlling dispersion is the important theory of prevention and treatment of liver fibrosis, under the guidance of the theory, Sinisan Jiawei prescription has a good therapeutic effect on rat liver fibrosis model.2. Sinisan Jiawei prescription has good functions of protecting liver cells, anti-inflammatory, reducing enzymes to improve liver. The dose group of Sinisan Jiawei, the prevention group of Sinisan Jiawei has significant effect to reduce liver fibrosis model rats serum alanine aminotransferase (ALT), glutamic-oxalacetic transaminease (AST), GGT and ALP activity, and can significantly reduce liver fibrosis models of rats serum HA, III collagen type, these embody Sinisan Jiawei prescription’s effect of "soothing-liver regulating qi, invigorating spleen and supplementing qi, soften hard lumps and dispel nodes" and the scientific of the theory of "liver controlling dispersion". 3. Sinisan Jiawei prescription can reduce the rat liver tissue’s expression amount of TGF beta1, TGFRmRNA, HA protein and protein expression, and through various channels, its mechanism may reduce TGF-beta1and TGFR expression in order to decrease hepatic stellate cell activation, control TGF beta1signaling pathways, reduce the generation of the ECM and reduce the generation of HA, so that it can play the part of anti-liver fibrosis and protecting the liver cell damage.4. Sinisan Jiawei prescription can reduce the expression amount of Rhoam gene and protein, a-SMA protein of liver tissue in rat liver fibrosis model, and more significant is the reducing of amount about Sinisan Jiawei dose group, Sinisan Jiawei prevention Rhoam gene and protein expression, and a-SMA protein expression. These confirm that Sinisan Jiawei effect mechanism of the treatment of liver fibrosis may be through the approaches such as cutting RhoA gene and protein expression, having the controlling effect on RhoA/ROCK pathway, reducing alpha SMA protein expression, restraining the hepatic stellate cell activation and migration, and so forth, thereby protect liver cell, and then play the role of anti liver fibrosis.