The Study On Combination Formula,Immunity Effects And Molecular Mechanisms Of Anti-fibrosis Herbs And Selenium On Rats With Hepatic Fibrosis

Hepatic fibrosis is a common pathological basis of various chronic hepatic diseases and the inevitable mediate stage to cirrhosis. Hepatic fibrosis is the common disease in China, as well as in the world, causing great affliction to patients. The main factor leading to cirrhosis in western countries is alcohol, while virus hepatic in China. According to the serum epidemiological survey on hepatitis, the positive rate of HbsAg is 9.75% which results in high incidence rate of hepatitis. About 160,000 patients died of cirrhosis and liver cancer developing from hepatitis every year.The present studies indicate that hepatic fibrosis is reversible. If patients can be treated properly in this stage, cirrhosis could be prevented successfully. However, there is no ideal anti-fibrosis drug up to date all over the world. Chinese herbs, well known for their definite effectiveness, cheap prices and negligible side effects, have particular advantages in therapeutic research of hepatic fibrosis. Orthogonal test is an effective, economical multifactor design method. There is rare study on Chinese herb combination formula using orthogonal test till now. As we know Chinese herb have a definite effects on immune function. Selenium is also involved in immune response and affects metabolism of other microelement in body. There seems no study on treatment of hepatic fibrosis using Chinese herb and selenium so far.Many studies suggest that cytokines play important roles during hepatic fibrosis with different mechanisms. The transforming growth factorβ1 (TGF-β1)is the most powerful cytokine to promote fibrosis. TGF-β1 has been considered to be the key factor in acceleration of the cirrhotic procession and over expression of this cytokine is closely associated with fibrogenesis in many ways. NF-(B is known to be a family of dimeric transcription factors. It is ubiquitously expressed in non-B cells as an inactive form sequestered in cytoplasm by binding to specific inhibitory proteins termed I-(B. When inducing agent's stimulate cells, the I-(B became phosphorylated, ubiquitinated, and degraded. Degradation of I-(B can free NF-(B, which is then translocated into the nucleus, where it activates transcription. NF-(B/Rel has been shown to be implicated in the inflammatory response. Furthermore, NF-(B has been found to be related to cell proliferation and transformation. Study on treatment of fibrosis using Chinese herb by down-regulated the expression of TGF-(1, down-regulation the activity of NF-(B/Rel is so little that there is no systematic study so far. In order to solve these problems,this research was designed to explore the combination formula of anti-fibrosis herb using Orthogonal test, to evaluate the effects of immune function of the anti-fibrosis herb and selenium, to find out the possible molecular mechanisms from gene level and protein level. Part 1 The Experiment Study on Combination Formula ofAnti-Fibrosis Herbs and the Treatment Effects ofOptimized Herbs and Selenium Objective:To explore the best combination formula of anti-fibrosis herb using orthogonal test. To compare the treatment effect of optimized herbs and selenium. Methods: The hepatic fibrosis model was developed by complex factors including subcutaneous injecting CCl4 and feeding high fat food to SD rats. Repeating orthogonal design L16 (215), 6 factors (7 herbal ingredients), 2 level (use and disuse) was used. After modeling, the rats were divided randomly upon L16(215) orthogonal table into the groups and were given drugs orally for six weeks. Alanine transaminase(ALT),albumin(ALB),hepatic hydroxy proline (Hyp) and hyaluronic acid(HA) were examined. The herbal ingredients with remarkable function were selected which composing anti-fibrosis Ⅱ and Ⅲ. SD rats were divided randomly into 10 groups(10 rats per group): Control group, Hepatic fibrosis model group, Hepatic fibrosis model with natural recovery group, Colchicine group, Anti-fibrosis Ⅰgroup, Anti-fibrosis Ⅰplus selenium group, Anti-fibrosis Ⅱgroup, Anti-fi...