| Objective: To study the effect of insulin resistance (IR) andKupffer Cell (KCs) disorder on the occurrence of Nonalcoholic FattyLiver Disease (NAFLD); to compare the prevention and therapy effect ofpioglitazone(PIO) on NAFLD; to explore the mechanisms of PIO onNAFLD.Method:Seventy-two male SD rats were randomly divided into sixgroups (n=12):the normal control group that sacrificed on the 8th week(NG8W),the fat-diet group that sacrificed on the 8th week(FG8W) andthe PIO group that sacrificed on the 8th week(PIO prevention group); thenormal control group that sacrificed on the 12th week(NG12W),the fat-diet group that sacrificed on the 12th week(FG12W) and the PIO groupthat sacrificed on the 12th week(PIO treatment group). NG8W andNG12W fed with a standard diet and treated with vehicle for the last 4weeks before sacrificed, FG8W and FG12W fed with a high-fat diet andtreated with vehicle for the last 4 weeks before sacrificed, PIO preventiongroup and PIO treatment group fed with a high-fat diet and treated withPIO 10mg.kg-1·d-1 for the last 4 weeks before sacrificed. All drugs or veh-icle were administered by stomach tube ltime.day-1.Body weight was me-asured before sacrificed.8 SD rats were randomly choiced out from eachgroup,collect blood from the abdominal aorta, the levels of alanine amin- otransferase(ALT),aspartate aminotransferase(AST), triglyceride(TG),total cholesterol(TC),fasting plasma glucose(FPG),fasting insulin(FIns)were measured,and fasting insulin resistance index(FIRI) was calculated.liver weight was measured and liver index was calculated.The assessmentof hepatic steatosis and inflammatory activity in all rats were scord acco-rding to criteria under light microscope.Collected KCs from the rest 4 ratsof each group,the levels of tumor necrosis factor-α(TNF-α)and nitricoxide(NO)secreted by KCs was measured.Result:(1)The liver index, the levels of ALT,AST,TG,TC,Flns, FIRI,the levels of TNF-αand NO secreted by KCs in the FG8W and FG12Wwere higher than NG8W and NG12W,there was difference between thesegroup (p＜0.05). Histological changes demonstrated that rats of FG8Wand FG12W developed diffuse hepatic steatosis and lobular inflammatorycell infiltration.KCs were bigger in these groups.(2)The liver index, thelevels of ALT,AST, TG,TC, FIns,FIRI and the levels of TNF-α,NOsecreted by KCs in the PIO prevention group were lower than theFG8W,there was differrence between these two groups(p＜0.05),therewas no difference between the PIO prevention group and theNG8W(p＞0.05). The histological and the KCs demonstrated of the PIOprevention group was much similar with NG8W.(3)The liver index, thelevels of ALT,AST,TG,TC,FIns and FIRI of the PIO treatment groupwere lower than FG12W,there was difference between the PIO treatment group and the FG12W(p＜0.05),the liver index, the levels of ALT,ASTwere still higher than NG12W,there was difference between the PIOtreatment group and the NG12W(p＜0.05),there was no difference inTG,TC,FIns and FIRI between the PIO treatment group and the NG8W(p＞0.05). The level of TNF-α,NO secreted by KCs of the PIO treatmentgroup had no difference with FG12W(p＞0.05).The histological changesdemonstrated that hepatic steatosis was improved in the PIO treatment gr-oup,but there were still a lot of lobular inflammatory cell infiltration.KCsstill bigger than NG12W.(4)There is a postive correlations betweenFIRI ,the lever of TNF-α,NO secreted by KCs and the NAFLD score:thehepatic steatosis score and HAI.Comclusions:There may be a relationship between IR, KCs disorderand the occurrence of NAFLD;PIO have a good effect on the inhibitionand trentment of NAFLD;the PIO prevention group have a better effecton the occurrence and development of NAFLD than the PIO treatmentgroup;the mechanisms that PIO prevent and treat NAFLD maybe haverelationships with improve IR, modulate lipometabolism,and prevent thebeginning KCs disorder.
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