白芍总苷对NAFLD大鼠HMGB1，TLR4通路的干预作用

目的:探讨白芍总苷(TGP)对高脂-果糖诱导非酒精性脂肪性肝病(NAFLD)大鼠肝组织中高迁移率族蛋白1(HMGB1),Toll样变体4(TLR4)信号通路的影响及其作用机制。方法:用高脂-高果糖餐诱导NAFLD大鼠模型,除设正常组外,将模型大鼠随机分为模型组,水飞蓟宾组,二甲双胍组(200 mg·kg~(-1)·d~(-1)),TGP高、低剂量组(200,100 mg·kg~(-1)·d~(-1))。用药6周后观察各组大鼠空腹血糖(FBG),餐后2 h血糖(2 hBG),胰岛素(Fins),总胆固醇(TC),低密度脂蛋白胆固醇(LDLC),高密度脂蛋白胆固醇(HDL-C),甘油三酯(TG),游离脂肪酸(FFA),丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)水平,计算胰岛素抵抗指数(HOMA-IR)和肝脏指数;并以免疫蛋白印迹法(Western blot)检测肝组织中HMGB1,TLR4蛋白的表达。结果:与正常组比较,模型组转氨酶,肝脏指数,血脂,2 hBG,Fins,HOMA-IR及TLR4,HMGB1蛋白均明显升高(P0.05,P0.01);与模型组比较,TGP高、低剂量组2 hBG,Fins,HOMA-IR,LDL-C,TG,TC,FFA,ALT,AST均明显降低(P0.05,P0.01),高、低剂量TGP在拮抗胰岛素抵抗、降糖降脂,改善肝功能有较显著的作用,TGP高、低剂量组均可下调HMGB1,TLR4蛋白的表达(P0.01)。结论:在NAFLD病程进展中,HMGB1,TLR4是导致炎症的其中一条通路,TGP通过下调HMGB1,TLR4信号通路的表达而起到抑制大鼠NAFLD炎症发展的作用。

Effect of Total Glucosides from Paeoniae Radix Alba on HMGB1,TLR4 Pathway in Rats with Nonalcoholic Fatty Liver Disease

Objective: To investigate the effect and mechanism of total glucosides from Paeoniae Radix Alba(TGP) on high mobility group protein 1(HMGB1),Toll like receptor 4(TLR4) signal pathway in non-alcoholic fatty liver disease(NAFLD) rats induced by high fat and fructose feed. Method: high fat and high fructose diet was used to establish NAFLD rat models. All the rats except those in normal group were randomly divided into model group, silymarin group (200 mg·kg^-1·d^-1), metformin group (200 mg·kg^-1·d^-1), TGP high and low dose groups (200, 100 mg·kg^-1·d^-1). Rats were observed after 6 weeks of treatment, including fasting blood glucose (FBG), 2 hour postprandial blood glucose (2 hBG), insulin (Fins), cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) level and insulin resistance index (HOMA-IR) and liver index. In addition,HMGB1 and TLR4 protein expression levels in liver tissues were detected by Western blot. Result: The aminotransferase, liver index, blood lipid, 2 hBG, insulin, HOMA-IR and TLR4, HMGB1 protein in model group were significantly higher than those in the normal group (P<0.05, P<0.01). As compared with the model group, 2 hBG, Fins, HOMA-IR, LDL-C, TC, TG, FFA, ALT and AST levels were significantly lower in both TGP high dose and low dose groups (P<0.05, P<0.05). Both high dose and low dose TGP showed significant effects in antagonizing insulin resistance, lipid-lowering, glucose-lowering, and improving liver function, and could down-regulate HMGB1/TLR4 protein expression levels (P<0.01). Conclusion: In the course of NAFLD progression, HMGB1,TLR4 is one of the pathways leading to inflammation, and TGP plays a role in inhibiting the development of NAFLD in rats by down regulating the expression of HMGB1,TLR4 signaling pathway.