Nonalcoholic Fatty Liver Tissue Of Hepatitis TNFA, TGFB1, Leptin And Mapk Expression And Drug Intervention

Objective:To study the effects of lipid metabolism、insulinresistanee(IR)、inflammatory reactionand singnaling pathways pathoathogenesis of NAFLD by establishing rat model of similarto human non-alcoholic fatty liver disease (NAFLD) with high-fat diet; to observe the effe-cts of valsartan on lipid metabolism、IR、inflammatory reaction and singnaling pathwaysin rats with NAFLD，and provide a theoretical basis for clinical drug treatment.Methods:After ordinary feed adaptability to feed one week,48male SD rats were randomly div-ided into two groups: normal diet group(NG,n=16), and high-fat diet group(MG,n=32).The NG were fed on normal diet and the MG were fed on high-fat diet. At the end of11thweek,8rats were randomly drew off from each group to confirm the NAFLD model,and these rats were named N group and M group.At the beginning of12thweek,all rats ofMG were randomly divided into3groups:M0(n=8),the rats of this group were sequentiallyfed on high-fat diet,and were given normal sodium chloride2ml every day for5weeks:die-t treatment group G0(n=8),the rats of this group were sequentially fed on normal diet,andwere given normal sodium chloride2ml every day for5weeks: valsartan treatment group(DG,n=8),the rats of this group were sequentially fed on normal diet,and were givenvalsartan16.8mg/kg/d for5week;N0(n=8) the rats of this group were sequentially fed onnormal diet,and were given normal sodium chloride2ml every day for5weeks. Afterfilling the stomach to continue raising a week, end the study.Rats were pointed cage feed-ing and freely water and eat food.Fasted and weighed all the rats before executing. Afterexecuting,serum triglyceride(TG)、total cholesterol(TC)、Low density lipoprotein (LDL)、fasting blood glucose(FBS)、fastinginsulin(Fins)、and were measured by drawing bloodfrom heart.Then the liver was dissoeiated and weighed.Fasting insulin resistance index (FIRI) was caleulated.The liver tissues were made to10%liver homogenate for measuringthe levels of TNFα、TGFβ1、Leptin、ERK1/2using ELISA. Paraffin section and H-E stainobserves the liver tissue steatosis degree.Masson observes the liver tissue fibrosis stage.Using the statistical analysis software SPSS13.0, P <0.05with a statistical significance.Results:48rats didn’t appear deaths in the process of feeding and all of them enter into theresult analysis.1. Compared to the corresponding period of NG the weight,liver wet weight, liverindex、serum TG,TC,LDL,FBS,FIRI,and hepatic tissue TNF-α, TGF-β1, Leptin, ERK1/2levels of MG were higher,there were significant statisties differences between them(P<0.05);2. The degree of hepatic steatosis、lobular inflammatory-cell infiltration、 hepatic cellballooning degeneration, hepatic fibrosis change: Vacuolar hepatic steatosis was observedin MG rats under the light microscope; the diffused hepatic steatosis、lobular inflammatory-cell infiltration and slight fibrosis were observed in M0rats under the light microscope;Hepatic steatosis、inflammatory-cell infiltration、fibrosis and necrosis significantly reducedin the G0group and G group.3. The levels change of TG、TC、 LDL:Compared with N0group, the levels of serumTG, TC, LDL of M0group were significantly increased, there were significant statisticsdifferences(P <0.05); Compared with M0group, the levels of serum TG, TC，LDL of G0and G group were significantly increased, there were significant statistics differences(P <0.05); Compared with G0group,the levels of serum TG, TC of G group were significantlyreduced, there were significant statistics differences(P <0.05).4. The change of serum FBS, FINS, FIRI: Compared with N0group,the levels ofserum FBS, FINS, FIRI of M0group were significantly increased,there were significantstatistics differences(P <0.05); Compared with M0group,the levels of serum FINS, FIRIof the G0and G group were significantly reduced, there were significant statistics different-ces (P <0.05). Compared with G0group,the levels of serum FBS, FINS, FIRI of the Ggroup were significantly reduced, there were significant statistics differences(P <0.05).5. The change of hepatic tissue TNF-alpha, TGF β1, Leptin, ERK1/2: Compared withN0group,the levels of hepatic tissue TNF alpha, TGF β1, Leptin, ERK1/2of M0groupwere significantly increased,there were significant statistics differences(P <0.05); Compar-ed with M0group,the levels of hepatic tissue ERK1/2of the G0group were significantly reduced, there were significant statistics differences(P <0.05). Compared with M0group,the levels of hepatic tissue TNF-alpha, TGF β1,ERK1/2of the G0group were significant-ly reduced, there were significant statistics differences(P <0.05). Compared with G0grou-p,the levels of hepatic tissue TNF alpha, TGF β1of the G group were significantlyreduced, there were significant statistics differences(P <0.05).Conclusions:1. The SD rat NAFLD model similar to human NAFLD process can be suecessfullyestablished by constantly feeding high-fat diet for10weeks.2. The hepatic tissue inflammation factor expressed increasly and the singnalingpathway of ERK1/2was restrained in the process of NAFLD;3. Compared with normal diet control group,valsartan can significantly reduce theinflammation factor of the hepatic tissue expression and improve IR and the signalingpathway of ERK and play therapeutic effect in SD rat NAFLD.