Study On Serum TNFα,Adiponcetin Level And The Expression Of Hepatic PPARγ Of Rats With Nonalcoholic Fatty Liver

Objectives: The prevalence of nonalcoholic fatty liver disease(NAFLD) is increasing year by year, this disease is not just liver steatosis, it can lead to end-stage liver disease. The pathogenesis is not entirely clear, and to date there are few effective drugs to heal it. This study aims to explore the role of TNFα, adiponcetin and peroxisome proliferator-activated receptor gamma (PPARγ) in its pathogenesis and to investigate the efficacy of traditional Chinese medicine- Ganzheng Fang (GZHF) in rats with NAFLD.Methods: 30 male Sprague-Dawley rats were divided into three groups randomly with 10 in each group after being fed with normal diet one week: Control group,Model group and Treatment group. Control group were fed with normal diet; model group and treatment group with fat-rich diet. All the experimental rats take food and drink water as their pleases. From the 13th week of model establishment, the rats in normal group and model group were treated with distilled water of 10 ml/kg once a day; while in treatment group10 ml/kg GZHF solution once a day.Sixteen weeks later, all the rats were sacrificed to detect levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) by using automatic biochemitry analyzer. The levels of Serum TNFαand Adiponectin was tested with radioimmunoassay. The level of steatosis was observed under light microscope after haematoxylin-eosin (HE) staining and inflammation activity was also scored. Western blotting and reverse transcription- polymerase chain reaction (RT-PCR) were used to observe the protein and mRNA expressions of hepatic PPARγ.The experimental data between both groups was compared by two-sampleaverage t test, while ranked data was adopted with rank sum test.Results:1. Body weight (g) and liver/body weight index: The mean body weight and liver/body weight index of model group (488.02±12.98 and 3.301±0.086%, respectively) were increased significantly compared with normal group (368.88±20.39 and 2.846±0.078%, respectively) (P﹤0.01). Compared with model group, the treatment group (426.95±10.071, 2.951±0.054%) were decreased markedly (P﹤0.01).2 . Pathology observed by HE stain:①The level of steatosis: Steatosis was not seen in normal group, while Model group liver cells occurred steatosis generally, steatosis severe lipid degeneration were found, the severity was disparity significant compared with normal group(P<0.01), Compared with model group,steatosis significant relieved in treatment group (P<0.01).②The level of inflammation: No inflammation cell infiltrated in normal group, while portal inflammation occurred in hepatic lobule of model group, with the higher score of inflammation activity than normal group (P<0.01), In addition, the inflammation activity was remarkably slighter in treatment group than in model group (P<0.01).3. Serum biochemical index:①ALT and AST: ALT and AST level (u/L) of model group (60.86±3.28,235.54±21.97 respectively) were increased significantly compared with normal group (20.31±3.89,131.53.55±9.23 respectively) (t= 25.18,13.8 respectively, P﹤0.01). Compared with model group, the treatment group (52.45±2.44,185.32±5.13 respectively) were decreased markedly (t=6.50,7.04 respectively ,P﹤0.01),②TNFα: model group (3.40±0.18) were increased significantly compared with normal group (1.35±0.09) (t=32.58, P﹤0.01), Compared with model group, the treatment group (1.57±0.11) were decreased markedly (t=27.48, P﹤0.01),③Adiponectin: model group (6.21±0.39) were decreased significantly compared with normal group (12.14±0.83) (t= 20.36,P﹤0.01), Compared with model group, the treatment group (9.33±0.45) were increased markedly (t=16.47, P﹤0.01).4. Expression of hepatic PPARγ: Compared with normal group, the expressions of PPARγprotein and mRNA in liver tissue were obviously decreased in model group (t =414.88,26.229, P<0.01). Compared with model group, the expressions of PPARγprotein and mRNA in liver tissue wereincreased significantly in treatment group (t = 84.319,5.848, P<0.01).Conclusion:1.The increasing of Serum TNFαand the decreasing of Serum Adiponectin play an important role in NAFLD.2. The reduction of expression of PPARγcan promote liver steatosis and inflammation.3. Ganzheng Fang can strikingly alleviate hepatic steatosis and inflammation. It is an effective medicament in the treatment of NAFLD. Ganzheng Fang may produce a marked effect by modulating the expression of PPARγ.