Effect Of Shugan Granules On Perosisome Proliferator-activated Receptor Gamma MRNA In Non-alcoholic Fatty Liver Disease In Rats

Objective: Non-alcoholic fatty liver disease (NAFLD) is a Clinicopathologic syndrome which is caused by many reasons except by alcohol and other Specific Liver damage reasons. The main features of NAFLD, which contains simple fatty liver, steatohepatitis and cirrhosis, is Diffuse bullous hepatocyte steatosis. Now the Pathogenesis of NAFLD is not clear, but many researches proved that it was closely related to the disorder of glucose metabolism and lipid Metabolism. Peroxisome proliferator-activated receptor, (PPAR)is a transcription factor which is activated by ligand. It belongs to the nuclear hormone receptor superfamily, and contains three subtypes:α,β,γ. The PPAR-γ, which can be activated by many fatty acids and their derivatives, is the main regulator to Adipocyte gene expression and insulin signaling between cells and is involved in adipocyte differentiation and the regulation of lipid metabolism. So the researchers pay more and more attentions to the role of PPAR-γin the pathogenesis of NAFLD. This research is aimed to investigate the effect of shugan granules on peroxisome proliferator-activated receptor gamma mRNA in non-alcoholic fatty liver disease induced by high-fat diet in rats.Methods: Sixty male SD rats were randomly divided into two groups: normal control group and experimental group. The normal control group was fed by normal diet and the experimental group was fed by high fat diet (88% normal diet + 10% lard + 2% cholesterol). All the rats ate and drank freely. At the end of the twelfth week, the experimental group was randomly divided into five subgroups: rosiglitazone group, shugan granules high-dose group, shugan granules medium-dose group and shugan granules low-dose group. From the 13rd week, the normal control group and model group of rats were lavaged with distilled water 1ml/100g; the rosiglitazone group of rats were lavaged with rosiglitazone 0.4mg·kg^-1·d^-1; the shugan granules high-dose group of rats were lavaged with shugan granules 3g·kg^-1·d^-1; the shugan granules medium-dose group of rats were lavaged with shugan granules 2.5g·kg^-1·d^-1; the shugan granules low-dose group of rats were lavaged with shugan granules 2g·kg^-1·d^-1. At the end of 16th week, we killed all the rats and collected serums and liver tissues. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), alkaline phosphatase (ALP), triglyceride (TG), high density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids (FFA), adiponectin (ADI), tumor necrosis factor alpha (TNF-α), hyaluronic acid (HA) were investigated. Histopathological changes of liver were observed. The mRNA of Perosisome proliferator-activated receptor gamma in the liver was detected.Results: 1. Serum biochemical indicators:①transaminase: The ALT, AST, CHE and ALP significantly increased in the model group rats compared with in the normal control group rats. There was a significant difference between the two groups (P<0.01). After drug treatment, the ALT, AST, CHE and ALP decreased in varying degrees. The differences were significant compared with the model group (P<0.01 or P<0.05).②lipid: The TG and LDL increased significantly, HDL decreased significantly in the model group rats. There was a significant difference between the model group and the normal control group (P<0.01). After drug treatment, the TG and LDL decreased, the HDL increased in varying degrees. The differences were significant compared with the model group (P<0.01).③Serum adiponectin (ADI): The ADI decreased significantly in the model group rats. There was a significant difference between the model group and the normal control group (P<0.01). After drug treatment, the ADI increased in varying degrees. The differences were significant compared with the model group (P<0.01).④Serum Free fatty acids (FFA): The FFA increased significantly in the model group rats. There was a significant difference between the model group and the normal control group (P<0.01). After drug treatment, the FFA decreased in varying degrees. The differences were significant compared with the model group (P<0.01).⑤Serum Tumor necrosis factorα(TNF-α): The TNF-αincreased significantly in the model group rats. There was a significant difference between the model group and the normal control group (P<0.01). After drug treatment, the TNF-αdecreased in varying degrees. The differences were significant compared with the model group (P<0.01).2. Pathology were observed by HE stain:①The degree of fatty degeneration: There was no fatty degeneration in the normal control group rats'liver cells. There was widespread fatty degeneration in the model group rats'liver cells which contained large fat droplets. The difference between the normal control group and the model group was significant (P<0.01). The lipid droplets in the liver cells were reduced significant in the treatment groups. The degree of fatty degeneration, compared with model group, was significant different (P<0.01 or P<0.05).②Inflammation: There was no inflammatory cell infiltration in the normal group rats'liver cells. Portal inflammation occurred in hepatic lobule of model group, with higher score of inflammation activity than normal group (P<0.01). In addition, the inflammation activity was remarkably slighter in the treatment group than in model group (P<0.01).3. Expression of hepatic PPAR-γmRNA: Compared with normal group, the expression of PPAR-γmRNA in liver tissue was obviously decreased in model group (P<0.01). Compared with model group, the expression of PPAR-γmRNA in liver tissue was increased significantly in treatment group (P<0.01). Conclusion: 1. The increasing of serum TNF-αand serum FFA play an important role in NAFLD, while the decreasing of serum ADI play an important role in NAFLD too.2. The expression of PPAR-γmRNA declines in the liver in NAFLD.3. Shugan granules can lower blood lipids, reduce inflammation of the liver and the degree of fatty degeneration, Anti-hepatic fibrosis and its molecular mechanisms are possible by activating the expression of PPAR-γto play a role.