摘要
目的 观察罗格列酮和二甲双胍对大鼠非酒精性脂肪肝病(NAFLD)的预防作用,并探讨其可能作用机理。方法 32只雄性SD大鼠分为4组:正常对照组、NAFLD对照组、罗格列酮干预组、二甲双胍干预组。以高脂饲料饲养诱发脂肪肝大鼠模型。12周末,处死所有动物,检测血脂、肝功能、肝脂质含量、肝组织病理学等,并检测血肿瘤坏死因子α(TNF-α)及肝组织TNF-α、肉毒碱软脂酰转移酶Ⅰ(CPT—Ⅰ)、乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(FAS)的mRNA表达等指标。结果 与NAFLD对照组比较,罗格列酮干预组及二甲双胍干预组的血TG(0.55±0.08,0.71±0.15 vs 0.85±0.15)mmol/L、ALT(49.1±7.4,56.0±33.6vs110.6±44.2)U/L及肝组织TG含量(33.7±8.2,37.2±7.8vs54.8±7.6)mg/g均显著下降(P均〈0.05),其肝脂肪变性及炎症程度亦显著减轻,其血清TNF-α(187.5±20.3,211.9±26.6vs324.2±34.2)pg/ml及肝组织TNF-α(0.35±0.12,0.49±0.18vs0.85±0.20)、FAS mRNA表达水平(0.34±0.13,0.45±0.15vs0.68±0.19)亦显著下降(P均〈0.05)。结论 罗格列酮和二甲双胍,可对高脂饲料饲养诱发的大鼠NAFLD产生保护作用;其保护作用与减少TNF-α和FAS表达有关。
Objective To investigate the preventive effects of rosiglitazone and metformin on nonalcoholic fatty liver disease (NAFLD) in rats, and explore the possible mechanisms involved. Methods Thirty-two male SD rats were randomized into normal control group, NAFLD control group, rosiglitazone-prevention and metformin-prevention groups. NAFLD rat model was established by feeding with high caloric diet. Serum TC, TG, ALT, AST, TNF-α, and liver lipid contents, liver histology and liver mRNA expressions of TNF-α, earnitine palmityl transferase - 1 (CPT-1). acyl- COA earboxylase (ACC) and fatty acid synthase (FAS) were assayed at the end of the 12 th week. Results Compared with NAFLD control group, rosiglitazone-prevention and metformin-prevention groups serum TC(0. 55±0. 08,0. 71±0. 15 vs 0.85±0.15)mmol/L, ALT(49.1±7.4,56.0±33.6 vs 110. 6±44. 2)U/L, and liver TG(33.7±8. 2, 37.2±7.8 vs 54.8±7.6)mg/g decreased significantly (P〈0. 05) ; fatty denaturation of liver tissues and hepatic inflammation markedly reduced; and serum TNF-α(187.5±20. 3,211.9±26.6 vs 324.2±34. 2)pg/ml and liver TNF-α(0. 35±0. 12,0. 49±0. 18 vs 0. 85 ± 0. 20), FAS mRNA (0. 34 ± 0. 13,0. 45 ± 0. 15 vs 0. 68± 0. 19)also decreased significantly (P〈0. 05). Conclusions Rosiglitazone and metformin have protective effects on NAFLD in rats, and these effects may be related to the decreased expressions of TNF-α and FAS.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2007年第1期51-55,共5页
Chinese Journal of Geriatrics
基金
国家人事部博士后基金(2004036431)
关键词
脂肪肝
非酒精性
预防
胰岛素抵抗
Fatty liver, nonalcoholic disease
Prevention
Insulin resistance