【摘要】 目的:探讨六味地黄丸对妊娠期糖尿病(GDM)胰岛素抵抗的miR-103调控机制。方法:随机数字表法将60只雌性大鼠分为对照组、GDM模型组、六味地黄丸低剂量组、六味地黄丸高剂量组,每组各15只,比较四组血糖水平、胰岛素抵抗指数(HOMA-IR),采用实时定量PCR技术(qRT-PCR)、荧光定量PCR、蛋白质印迹法(Western blot)等方法检测四组miR-103、小窝结构(Caveolae1)-胰岛素受体底物(IRS)-磷酸化蛋白激酶B (p Akt)信号通路相关基因和蛋白表达水平。结果:六味地黄丸高剂量组FBG、INS、HOMA-IR和miR-103表达水平较GDM模型组和六味地黄丸低剂量组明显低,差异显著(P<0. 05);六味地黄丸高剂量组Caveolae1、IRS、p Akt相关基因表达水平和其蛋白表达活性较GDM模型组和六味地黄丸低剂量组明显高,差异显著(P<0. 05);六味地黄丸高剂量组上述各项指标与对照组相比较差异无统计学意义(P>0. 05)。结论:六味地黄丸对GDM临床疗效明确,作用机制可能与其有效下调miR-103水平,从而抑制miR-103调控靶基因Caveolae1、IRS和p Akt有关。更多还原

【Abstract】 Objective: To investigate the miR-103 regulatory mechanism of Liuwei Dihuang Pills on insulin resistance in gestational diabetes mellitus( GDM) rats. Methods: 60 female rats were randomly divided into control group,GDM model group,low-dose Liuwei Dihuang Pills group and high-dose Liuwei Dihuang Pills group,15 rats in each group. Blood glucose levels and insulin resistance index( HOMA-IR) were compared among the four groups. The expression levels of miR-103,caveolae structure( Caveolae1)-insulin receptor substrate-1( IRS)-phosphorylated protein kinase B( p Akt) signal pathway related genes and proteins in the four groups were detected by the real-time quantitative PCR technique( qRT-PCR),fluorescence quantitative PCR and Western blot. Results: The expression levels of FBG,INS,HOMA-IR and miR-103 in the high-dose Liuwei Dihuang Pills group were significantly lower than those in the GDM model group and the low-dose Liuwei Dihuang Pills group( P < 0. 05). The expression levels of Caveolae1,IRS and p Akt related genes and their protein expression activities in the high-dose Liuwei Dihuang Pills group were significantly higher than those in the GDM model group and the low-dose Liuwei Dihuang Pills group( P < 0. 05). There was no significant difference between the high-dose Liuwei Dihuang Pills group and the controlled group in above-mentioned indexes( P > 0. 05). Conclusion: The curative effect of Liuwei Dihuang Pills on GDM is clear. The mechanism of action may be related to the effective down-regulation of miR-103 levels,thus inhibiting miR-103 regulating target genes Caveolae1,IRS and p Akt.更多还原