基于TXNIP/miR-204/MAFA信号通路探讨糖异平调控糖耐量减低胰岛β细胞的机理研究

Impaired of islet β cell function is a key factor in the pathogenesis of impaired glucose tolerance(IGT). Our previous study revealed that the effect of Tang yi ping with the function of invigorating spleen and regulating liver, resolving phlegm and activating blood in treating IGT was associated with epigenetic modification and metabolism of β cell by TXNIP/miR-204/MAFA signaling pathway.To further explore the mechanism of improving the function of islet β cells by the signaling pathway, this study will apply the combination vivo with vitro methods. In vivo experiments the IGT model rats were established，After intervention of Tang yi ping , observing the influence of Tang yi ping on phosphorylation, on phosphorylated cytokine protein, the expression of mRNA, protein mass spectrometry ，and mirna expression of he pancreas tissue in the TXNIP/miR-204/MAFA signaling pathway of IGT rat islet cells.In vitro experiment，we use miR-204inhibitors to Silence miR-204 expression to verify the influence of serum containing Tang yi ping on the expression of related factors of islet beta cells and microRNA under the circumstance of lack of TXNIP/miR-204/MAFA signaling pathway.The study illustrates the influence of Tang yi ping on the improvement of islet β cell by TXNIP/miR-204/MAFA signaling pathway, and the mechanism of molecular and the effect of target of Tang yi ping, which provided the scientific pursuant of treating IGT by Traditional Chinese Medicine.

胰岛β细胞功能受损是IGT发病的关键环节，我们前期实验表明，具有健脾调肝、化痰活血功效的糖异平治疗IGT的作用与表观遗传修饰及TXNIP/miR-204/MAFA信号通路有关。为进一步探讨糖异平通过该信号通路改善胰岛β细胞的作用机制，本研究拟采用体内和体外实验相结合，体内实验通过建立大鼠IGT模型，给予糖异平干预后，分析大鼠不同时相胰岛功能、各磷酸化和非磷酸化细胞因子蛋白量、mRNA表达、蛋白质谱及MicroRNA表达谱的变化。体外实验通过沉默miR-204表达，验证糖异平含药血清对缺失TXNIP/miR-204/MAFA信号的胰岛β细胞相关因子的表达及MicroRNA表达的影响，进一步证实是TXNIP/miR-204/MAFA信号通路介导了糖异平含药血清对胰岛β细胞的调控作用。进而客观的从表观遗传和分子水平探讨糖异平治疗IGT的作用机理，为中医药治疗IGT提供科学依据。

胰岛β细胞功能受损是IGT发病的关键环节，我们前期实验表明，具有健脾调肝、化痰活血功效的糖异平治疗IGT的作用与表观遗传修饰及TXNIP/miR-204/MAFA信号通路有关。为进一步探讨糖异平通过该信号通路改善胰岛β细胞的作用机制，本研究拟采用体内和体外实验相结合，体内实验通过建立大鼠IGT模型，给予糖异平干预后，分析大鼠不同时相胰岛功能、各磷酸化和非磷酸化细胞因子蛋白量、mRNA表达、蛋白质谱及MicroRNA表达谱的变化。体外实验通过沉默miR-204表达，验证糖异平含药血清对缺失TXNIP/miR-204/MAFA信号的胰岛β细胞相关因子的表达及MicroRNA表达的影响，进一步证实是TXNIP/miR-204/MAFA信号通路介导了糖异平含药血清对胰岛β细胞的调控作用。进而客观的从表观遗传和分子水平探讨糖异平治疗IGT的作用机理，为中医药治疗IGT提供科学依据。