脂联素对非酒精性脂肪性肝炎的作用及其机制

THERAPEUTIC EFFECT OF ADIPONECTIN ON NONALCOHOLIC STEATOHEPATITIS AND THE UNDERLYING MECHANISMS

目的探讨脂联素对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)的治疗作用及其机制。方法给予NASH大鼠5周脂联素治疗后,取血液及肝脏标本进行肝湿质量、肝三酰甘油(triglyceride,TG)含量及血清学相关指标检测,天狼星红-苦味酸染色法观察肝组织病理形态学变化。同时检测血清肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)及肝组织TNF-α mRNA表达水平;α-平滑肌肌动蛋白(α-Smooth muscle actin,α-SMA)免疫组织化学染色用以观察脂联素对肝组织肝星状细胞(hepatic stellate cell,HSC)活化的影响。结果给予脂联素治疗后,NASH大鼠肝湿质量、肝脏TG值与模型组比较显著降低(P<0.05),血清学指标天冬氨酸氨基转移酶、丙氨酸氨基转移酶、TG、总胆固醇、透明质酸、血糖、胰岛素等显著改善,脂肪肝Brunt分级有显著降低(P<0.05);血清TNF-α水平及肝组织TNF-α mRNA表达显著降低(P<0.05),α-SMA免疫组织化学染色显著降低(P<0.05)。结论脂联素可通过改善胰岛素抵抗、抑制炎性因子TNF-α表达和HSC活化等多个途径治疗NASH。

Objective To investigate the therapeutic effect of adiponectin on nonalcoholic steatohepatitis(NASH)and the underlying mechanisms.Methods After 5 weeks' adiponectin therapy,the sera and hepatic tissues of NASH rats were harvested.Hepatic wet weight,hepatic triglyceride(TG).serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),TG, cholesterol(CHO),blood sugar,insulin,hyaluronic acid(HA)were measured.The character of hepatic histology,the level of serum TNF-α and hepatic TNF-α mRNA expression and the expression of hepatic α-Smooth muscle actin(α-SMA)were detected.Results After adiponectin therapy,the hepatic wet weight and hepatic TG of NASH rats were decreased obviously.AST, ALT,CHO,TG,HA,blood sugar,insulin were significantly ameliorated.Brunt scores of steatosis,serum TNF-α levels,hepatic TNF-α mRNA expression and the level of α-Smooth muscle actin(α-SMA)expression were all decreased in therapeutic group(P<0.05). Conclusion Adiponectin has an obviously therapeutic effect on NASH through interfering in several key points in the development of NASH,including insulin resistance,expression of TNF-α and hepatic stellate cell(HSC)activation.