姜黄素对非酒精性脂肪肝大鼠肝11β-HSD1表达及胰岛素抵抗的影响

Effect of curcumin on hepatic 11β-HSD1 expression and insulin resistance in rats with nonalcoholic fatty liver disease

目的观察姜黄素对非酒精性脂肪肝(NAFLD)大鼠肝11β-羟基类固醇脱氢酶1(11β-HSD1)表达及胰岛素抵抗的影响。方法大鼠随机分为4组:对照组、模型组、姜黄素低剂量组(C1组)、姜黄素高剂量组(C2组),高热量饲料喂养8周建立大鼠NAFLD模型,C1、C2组(姜黄素200、400 mg/(kg·d))治疗8周。实验结束后进行相关指标检测。结果姜黄素治疗可以降低肝指数,改善肝功能,降低血脂及肝脂质沉积,减轻肝组织病理改变,同时显著改善胰岛素抵抗状态且以上治疗作用呈剂量依赖性。肝组织11β-HSD1 mRNA及蛋白表达显示,C1组(0.157±0.013、0.264±0.062)和C2组(0.091±0.009、0.191±0.021)较模型组(0.264±0.015、0.477±0.074)均显著降低(P<0.05,P<0.01),且C2组更明显。结论姜黄素对高热量饲料所致大鼠NAFLD有较好治疗作用,可能与其抑制11β-HSD1表达,进而改善胰岛素抵抗有关。

Objective To observe the effect of curcumin on hepatic 11β-hydroxysteroid dehydrogenase type 1( 11β-HSD1) expression and insulin resistance in rats with nonalcoholic fatty liver disease( NAFLD). Methods Thirtytwo male Wistar rats were randomly divided into four groups: control,NAFLD model,low-dosage curcumin treatment( C1)and high-dosage curcumin treatment( C2) groups. The NAFLD model was established by a high-fat/high-sugar diet. After 8 weeks of the diet,the C1 and C2 groups were given 200 and 400 mg/( kg·d) curcumin,respectively,by intragastric administration for 8 weeks. Results Compared with the model group,the NAFLD was significantly improved in the C1 and C2 groups,expressed as the reduction of the fatty liver index,serum lipids,liver lipid deposition,improvement of liver function and pathological changes. Insulin resistance was also significantly improved. The relative expression levels of 11β-HSD1 mRNA and protein in liver tissue were significantly lower in the C1( 0. 157 ± 0. 013 and 0. 264 ± 0. 062,respectively) and C2 groups( 0. 091 ± 0. 009 and 0. 191 ± 0. 021,respectively) than those in the model group( 0. 264 ±0. 015 and 0. 477 ± 0. 074,respectively)( P < 0. 05,P < 0. 01). All curcumin treatment effects were dose-dependent.Conclusions Curcumin significantly improved NAFLD in rats,and this effect may be related to the inhibition of 11β-HSD1 expression and the improvement of insulin resistance.