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  

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

作　　者：王文平[1] 王佑民[1] 王丽萍[1] 

机构地区：[1]安徽医科大学内分泌代谢病研究所.第一附属医院内分泌科,安徽合肥230022

出　　处：《中国药理学通报》2008年第2期265-268,共4页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金资助项目(No03043719;070413080)

摘　　要：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。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）, highfat 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 lOmg/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 index, HOMA-IR and liver index were calculated. Pathologic histology and HE stain of rat livers were ob- served. Results Compared with HF group with NC group, body weight, liver index, levels of serum glu-cose, 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 obe- sity, 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.

关 键 词：关键词:大鼠 吡格列酮 脂联素 肿瘤坏死因子or 非酒精性脂肪肝 

分 类 号：R-332[医药卫生] R322.47