Research On The Effects Of Fenofibrate On Rats With Nonalcoholic Fatty Liver Disease

Object:To discuss the effects of insulin resistance(IR),lipid metabolism and inflammatory reaction on pathogenesis of NAFLD by establishing a rat model of nonalcoholic fatty liver disease(NAFLD) with high-fat diet;To observe the effects of Fenofibrate on IR,lipid metabolism and inflammatory reaction in rats with NAFLD,the curative effect on NAFLD,study its possible mechanism,and provide a reference for clinical drug treatment.Methods:Forty male SD rats were randomly divided into two groups:the normal diet group(n=16),which were fed on normal diet, and the high-fat diet group(n=24),which were fed on high-fat diet(normal diet adding 1%cholesterol and 14%lard).At the end of 8^th week,8 rats were randomly drew off from each group to identify the NAFLD model, these two groups were named the normal diet group that sacrificed on the 8th week(NG8w),and the high-fat diet group that sacrificed on the 8th week(HG8w).At the beginning of 9^th week,the rest of the rats in the high-fat diet group were randomly divided into two groups:the high-fat diet group that sacrificed on the 12th week(HG12w) and the Fenofibrate group that sacrificed on the 12th week(FG),and the rest of the rats in the nomal diet group were sacrificed on the 12th week(NG12w).The NG12 and HG12 were given normal sodium chloride 2ml every day for the last 4weeks,the FG were given Fenofibrate 20mg/kg/d for the last 4 weeks. Fasted and weighed all the rats before executing,after executing,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),fasting blood glucose(FBS),fasting insulin(Fins),free fatty acids(FFAs) and tumor necrosis factor-α(TNF-α) were measured by drawing blood from portal vein;then, the liver was dissociated and weighed,fasting insulin resistance index (FIRI) was calculated;the liver tissues were made to 10%liver homogenate for measuring the levels of liver TG,TC,FFAs.Hepatic steatosis was assessed by using H-E stain sections,expression of PPARαof mRNA in liver tissue was detected by semi-quantitative method (RT-PCR).Result:(1) Compared to the corresponding period of the normal diet group,the weight,liver index,levels of serum Fins,FIRI,ALT,AST,TG,TC,FFAs,TNF-αand levels of liver homogenate TG,TC,FFAs of HG8w and HG 12w were higher,there were significant statistics differences between them(p＜0.05);Compared to HG12w rats,the weight,liver index,FIRI,levels of serum Fins,ALT,AST,TC,FFAs,TNF-αand levels of liver homogenate TG,TC,FFAs of FG were lower,but compared with NG12w,the results were Higher,there were significant statistics differences(p＜0.05);Serum TG level of FG was lower than HG12W,there were significant statistics differences(p＜0.05); However,there were no statistics differences between the Serum TG level of FG and NG12W;There were no statistics differences in FBS of each groups(p＞0.05).(2) Compared to the corresponding period of the normal diet group,the expression of PPARαof mRNA in liver tissue of HG8w and HG12w groups was lower,and the expression of the HG12w group rats is much lower than HG8w group;The expression of PPARa of mRNA in liver tissue of FG groups was higher compared to the HG12w group,but lower than NG12w group,there were significant statistics differences(p＜0.05);(3) Hepatic steatosis and balloon-like changes could be observed in HG8w rats under the light microscope;Diffuse hepatic steatosis and balloon-like changes with lobular inflammatory-cell were observed in HG12w rats;Hepatic steatosis and balloon-like changes also could be observed in FG rats,but compared to HG12w,the hepatic steatosis of FG were more less;(4)The expression of PPARαof mRNA showed a negative correlation with the detections expressing insulin resistance(IR),lipid metabolism and inflammatory reaction.Conclusion:1.The SD rat NAFLD model can be successfully established by constantly feeding high-fat diet for 8 weeks.2.Fenofibrate plays a therapeutic role in SD rat NAFLD.It provide a reference for clinical drug treatment.3.Fenofibrate can enhance the expressing of PPARα,then improve IR,adjusting lipid metabolism and anti-inflammatory,affect the development of NAFLD.