肥胖大鼠非酒精性脂肪肝与血清脂联素和肿瘤坏死因子α的关系及吡格列酮干预

目的观察营养性肥胖大鼠非酒精性脂肪肝(NAFLD)与血清脂联素和肿瘤坏死因子α(TNF-α)的关系,以及吡格列酮干预后的变化。方法45只SD♂大鼠随机分为3组:吡格列酮组(P)、高脂对照组(HF)和普通饮食组(NC),各15只。P、HF组给予高脂饮食,NC组给予普通饲料;12wk后,P组行吡格列酮10mg·kg-1.d-1灌胃,HF组和NC组用相应溶剂灌胃,均灌胃4wk。检测血清脂联素、TNF-α、游离脂肪酸(FFA)水平和其他生化指标等,计算Lee′s指数、HOMA-IR指数和肝脏指数,行肝脏病理切片和HE染色。结果与NC组相比,HF组大鼠体重、肝脏指数、FPG、FINS、ALT、HOMA-IR和血清TNF-α水平均明显增高,血清脂联素水平降低(P<0.05),肝细胞出现脂肪变性。与HF组比较,P组大鼠肝脏指数、HOMA-IR、FFA、TNF-α均降低,脂联素水平升高(P<0.05),肝细胞脂肪变性明显改善。HF组大鼠血清FFA、TNF-α与HOMA-IR、肝脏指数正相关,脂联素与之负相关(P<0.05)。结论高脂饮食可引起大鼠营养性肥胖、胰岛素抵抗和NAFLD;吡格列酮能提高胰岛素敏感性,改善脂肪细胞变性,可能与降低TNF-α、升高脂联素有关。

Relationship between nonalcoholic fatty liver disease and levels of serum adiponectin and tumor necrosis factor-α in obese rats and pioglitazone intervention

Aim To investigate the relationship between nonalcoholic fatty liver disease(NAFLD)and levels of serum adiponectin and tumor necrosis factor-α(TNF-α)in diet-induced obese rats and the effects of pioglitazone.Methods 45 SD male rats were randomly divided into three groups:pioglitazone group(P),high-fat diet group(HF),normal control group(NC),15 rats in each group.Rats in NC group were fed with standard food and the others with high-fat diet.After 12 weeks,rats in P group were treated with pioglitazone 10mg/kg ig daily for 4 weeks.Accordingly,HF and NC groups were administrated with homologous solvent.Serum adiponectin,TNF-α,free fatty acid(FFA),and biochemical data were observed,and Lee's index,HOMA-IR and liver index were calculated.Pathologic histology and HE stain of rat livers were observed.Results Compared with HF group with NC group,body weight,liver index,levels of serum glucose,insulin,FFA,ALT,HOMA-IR and TNF-α increased significantly,and serum adiponectin decreased(P<0.05).Liver steatosis was appeared in HF group.Compared with HF group,liver indices,the levels of HOMA-IR,FFA,and TNF-α lowered markedly,serum adiponectin elevated,and the liver steatosis were ameliorated in P group(P<0.05).Correlation analysis indicated that the levels of serum TNF-α,FFA in HF group rats were positively correlated with liver index and HOMA-IR(P<0.05),and adiponectin were negatively associated with them.Conclusion High-fat diet can induce alimentary obesity,insulin resistance and NAFLD.Pioglitazone can improve insulin sensitivity and alleviate liver steatosis.It may be associated with the decrease of serum TNF-α and the increase of adiponectin.