抗氧化微量营养素对T1DM小鼠Insulin基因表达的定量研究

Effects of united antioxidant micronutrients on transcriptional and translational expression of insulin gene of β cells in islets of T1DM mices

目的探讨联合抗氧化微量营养素(antioxidant micronutrients,AM)对胰岛β细胞insulin基因转录与翻译水平表达的影响,为应用天然抗氧化物的互补生物学作用,提高糖尿病状态下的胰岛素基因表达提供分子水平科学依据。方法应用MLDS(multiply low dosage of streptozotocin)方法制备T1DM小鼠模型,分别联合添加4种AM(Se+VE+V+Cr)和7种AM(Se+VE+V+Cr+VC+硫辛酸+烟酰胺)进行干预,运用ISH、IHC及图像分析技术系统观察其对insulin基因转录与翻译水平表达变化的影响。结果联合补充AM可明显增加T1DM模型小鼠胰岛β细胞insulin mRNA表达水平(P<0.05～0.01),提高胰岛β细胞insulin免疫组化阳性反应产物量(P<0.05～0.01),可分别在转录与翻译水平明显上调胰岛素基因的表达水平。结论 AM联合生物学效应可在转录与翻译水平上调T1DM时insulin基因表达,提高内源性胰岛素水平,拮抗糖尿病关键发病中间环节。

Objective To investigate the effects of united antioxidant micronutrients on transcriptional and translational insulin gene expression in isletsβ cells of T1DM mices and to design molecular tactis against diabetes from roles of naturel antioxidants in improving islet β cells functions.Methods T1DM mice model was made by injection of multiply low dosage of streptozotocin（MLDS）.The supplementation of united AM was designed two groups：AM4（Se＋VE＋V＋Cr） and AM7（Se＋VE＋V＋Cr＋VC＋lipoic acid ＋ niacinamide.The transcriptional and translational expression of insulin gene of β cells in T1DM mices were tested by ISH,PT-PCR,IHC,and immage analysis methods.Results Both AM4 and AM7 significantly increased the insulin mRNA expression as well as insulin-positive immune reactive production in β cells of T1DM mices（P0.05-0.01）.Conclusion The results suggest that The united AM may upregutate insulin gene expression not only in transcriptional level but also in translational level in β cells of T1DM mices,which may improve islet function and enhance endogenous insulin level in diabetes.