Study On The Effect And Mechanism Of Compound Zhenzhu Tiaozhi Capsule On Non-alcoholic Fatty Liver Disease In Rats

Objective: To observe the effect of compound Zhenzhu Tiaozhi capsule (FTZ) of non-alcoholic fatty liver disease (NAFLD) in rats and to investigate its mechanism, in order to support experimental evidence for further development and clinical application of FTZ.Methods: 60 SD rats were randomly divided into 6 groups: normal control group, model group, simvastatin group (4mg/kg), high (6g/kg), medium (3g/kg) and low (1.5g/kg) dose of FTZ group, 10 rats in each group. In addition to the control group, the other groups were administered high-fat emulsion in order to replicate the rat model of NAFLD. High-fat emulsion was given each morning, four hours later, high, medium and low dose of FTZ group and simvastatin group were administered 10ml/kg for the corresponding amount of drugs, meanwhile the control group and the model group were administered intragastrically with normal saline. All the rats were fed for 8 weeks. Weighed and observe the general condition of animals regularly during the experiment. At the end of the experiment, rats were anesthetized with 3.3% chloral hydrate in a dose of 10mL/kg. Anatomical changes and pathological changes in liver of each group were observed visually and by light microscopy, and liver index was calculated. Blood samples were collected for the determination of TC,TG,LDL-C,HDL-C,FFA,AST,ALT,fasting blood glucose(FBS), fasting insulin(FINS) and insulin resistance index (HOMA-IR). Liver samples were taken for assaying of TC,TG,SOD,MDA and measurement of the expression of LXRαmRNA and SREBP-1c mRNA. Results: Compared with model group, FTZ could significantly reduce lipid levels, FFA, the level of hepatic function, FBS, FINS, HOMA-IR, liver lipids, liver index, and liver MDA levels of serum in NAFLD rats, and all had significant difference (P <0.05 or P <0.01); but FTZ could significantly increased HDL-C in blood and liver SOD activity (P <0.05 or P <0.01); FTZ also significantly reduced the expression of LXRαmRNA and SREBP-1c mRNA in liver of NAFLD rats (P <0.05 or P <0.01).Conclusion: FTZ could effectively protect liver function and modulate lipid levels in NAFLD rats, so FTZ had obvious prevention and treatment to the experimental NAFLD rats. The possible mechanisms could be that: (1)FTZ could reduce the liver lipids and slow down the incidence and development of NAFLD rats by improving IR and reducing serum FFA and TG levels of liver; (2) FTZ could reduce the occurrence of lipid metabolism disorders by improving the antioxidant capacity of liver cells and metabolic balance of the free radical and inhibition of peroxidation injury on liver;(3) FTZ could reduce the over-expression of liver LXRαmRNA levels and reduce the expression of Enzyme gene for lipid synthesis in liver, thereby reducing the expression of SREBP-1c mRNA, so that the transport capacity of the liver and degradation of TG of hepatic accumulation were improved and serum FFA level was significantly reduced. As a result, the metabolism of fatty acid had been improved, and the occurrence and development of NAFLD had been eased.