青蒿琥酯对非酒精性脂肪肝小鼠肝脏TLR4及MyD88表达的影响

目的 观察青蒿琥酯对非酒精性脂肪肝病(NAFLD)小鼠肝脏Toll样受体4(TLR4)、髓样分化因子S8(MyD88)和磷脂酰肌醇-3激酶(PI3K)表达的影响.方法 70只昆明小鼠随机分为正常对照组、模型组、青蒿琥酯高60 mg/(kg·d)]、中30 mg/(kg ·d)]、低15 mg/(kg·d)]剂量组.采用高脂饲料构建NAFLD小鼠动物模型,于给药后12周末处死,观察肝脏病理变化,酶法检测血清三酰甘油(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)水平,RT-PCR法检测肝组织TLR4、MyD88、PI3K mRNA表达.结果 各青蒿琥酯剂量组小鼠血清TG、TC和ALT水平比模型组显著降低,肝脏脂肪变性明显减轻,肝组织TLR4、MyD88及PI3K表达量也显著降低(P＜0.01,P＜0.05).与正常对照组相比,模型组肝组织TLR4、MyD88及PI3K表达量显著升高(P＜0.01),且三者有相同的变化趋势.结论 TLR4/MyD88及其下游PI3 K/AKT通路可能在NAFLD发病中起重要作用.青蒿琥酯可通过降低TLR4、MyD88、PI3K mRNA表达,减轻NAFLD小鼠肝脏脂肪变性程度,降低血脂,改善肝功能指标.

Effect of artesunate on the expression of TLR4 and MyD88 in mice with non-alcoholic fatty liver disease

Objective To investigate the effects of artesunate on the expression of TLR4,MyD88 and PI3K in mice with non-alcoholic fatty liver disease.Methods 70 KM mice were randomly divided into the control group,model group,high 60 mg/(kg · d)],medium 30 mg/(kg · d)] and low 15 mg/(kg · d)] dosage of artesunate groups.Establishment of animal model of NAFLD mice by feeding with high fat diet.The appearance and pathological changes of liver was observed,serum triglyeride (TG),total cholesterol (TC),alanine aminotransferase (ALT) were detected by enzymic method.TLR4,MyD88 and PI3K in hepatic tissue were tested by RT-PCR after 12 weeks of administration.Results Compared with the model group:the level of serum TG,TC,ALT,and the expression of TLR4,MyD88 and PI3K in the artesunate groups were decreased significantly.The hepatic steatosis was ameliorated markedly (P ＜ 0.05,P ＜ 0.01).The expression of TLR4,MyD88 and PI3K in the model group were significantly increased compared with the control group(P ＜ 0.01).There was similar change tendency in the expression of TLR4,MyD88 and PI3K in hepatic tissue.Conclusion TLR4/MyD88 and PI3K/AKT,the downstream pathway,can play important role in the development of NAFLD.Artesunate can decrease the hepatic steatosis,and serum lipid,improve the index of liver function by decrease the expression of TLR4,MyD88,PI3K in hepatic tissue.