11β-HSD1抑制剂改善db/db小鼠胰岛素敏感性的实验研究

An 11β-HSD1 inhibitor improves insulin sensitivity in db/db mice

目的探讨11β-HSD1抑制剂H8对db/db小鼠胰岛素敏感性的影响。方法实验动物40只分成5个组,每组8只,分别是db/db对照组(Dia组)、罗格列酮组(Ros组)、姜黄素组(Cur组)、姜黄素类似物H8组(H8组)、db/m对照组(Con组)。H8灌胃给药42 d后尾静脉采血检测葡萄糖耐量(OGTT)、胰岛素耐量(IPITT);在第0、1、3、6周尾静脉采血检测空腹血糖值;眼球取血检测胰岛素抵抗系数(HOM A-IR);酶学检测肝脏、脂肪中11β-HSD1活性;ELISA法检测血清中糖皮质激素水平。结果 OGTT结果显示,与Dia组相比较,Ros组和H8组各时间点血糖值均有所降低;IPITT结果显示,相对于Dia组,Ros组和H8组血糖值均有所下降;空腹血糖在给药后第1~6周,H8组与Dia组比较明显降低;与Dia组比较,Ros组、Cur组和H8组胰岛素抵抗指数(HOMA-RI)明显降低(P<0.001);与Dia组对比,H8组可以明显的抑制肝脏(P<0.01)和脂肪(P<0.01)中11β-HSD1的活性;与Dia组对比,H8组GC水平降低(P<0.001)。结论 11β-HSD1的抑制剂H8可以降低db/db小鼠肝脏GC水平,进而提高胰岛素的敏感性。

Objective To explore the effects of H8,an inhibitor of 11β-HSD1,on insulin sensitivity in db/db mice.Methods A total of 40 db/db mice w ere divided into 5 groups： db/db model group（ Dia）,rosiglitazone treatment group（ Ros）,curcumin treatment group（ Cur）,curcumin analogues H8 treatment group（ H8）,and db/m control group（ Con）. H8 w as intragastriclly administered once per day for 6 w eeks,and then oral glucose tolerance test（OGTT） and intraperitoneal insulin tolerance test（IPITT） were performed at the end of the 6 th week. Fasting blood glucose levels,collected from the tail vein,w ere measured in 0 th,1 th,3 th,and 6 th w eek. At the end of the experiment,the inner canthus vein blood w as collected to examine HOM A-RI index. The activity of 11β-HSD1 in liver and adipocytes and the level of glucocorticoid in serum w ere detected w ith enzyme method and ELISA,respectively.Results The results of OGTT show ed that the blood glucose level w as significantly reduced in the Ros group and H8 group than in the Dia group. The IPITT results revealed that the blood glucose level w as significantly reduced in the Ros group and H8 group than in the Dia group. Fasting blood glucose level of H8 group w as significantly low er than that of Dia group from the 1 th to 6 th w eek after the treatment. The HOM A-IR indicator of the Ros group,Cur group and H8 group w as significantly low er compared w ith that of the Dia group（ P〈0. 001）. Compared w ith Dia group,H8 hadsignificantly inhibited 11β-HSD1 activity in liver（ P〈0. 01） and adipocytes（ P〈0. 01）,and reduced level of GC（P〈0. 001）. Conclusion H8,an 11β-HSD1 inhibitor,could reduce the hepatic GC level in db/db mice,thereby increasing the sensitivity of insulin.