黄芪多糖基于RACK1调节通路缓解LPS诱导的T2DM的研究

Endotoxemia can lead to the occurrence of T2DM. Lipopolysaccharide (LPS), the main component of endotoxin, can induce the excessive autophagy of islet β cells by regulating the RACK1/NF-KB pathway , which can trigger T2DM. However, it hasn’t been reported to alleviate LPS-induced T2DM by slowing down the excessive autophagy of islet β cells. The previous study of our research team found that Astragalus polysaccharides can inhibit the expression of LC3-I in islet β cells under condition of LPS stimulation and the expression of NF-KB in T2DM rats, but its specific mechanism is unclear. Our further pre-experiment discovered that Astragalus polysaccharides could upregulate the expression of RACK1 in islet β cells under LPS stimulation condition. Therefore, we suspect that Astragalus polysaccharides can slow down the occurrence of T2DM by regulating the RACK1/NF-KB pathway to block islet β cells excessive autophagy under LPS stimulation condition. In this study，we will explore the molecular mechanism of Astragalus polysaccharides to alleviate LPS-induced T2DM by LPS-induced T2DM rat model and gene overexpression, microRNA target gene validation and other molecular biology technology. The results can be further enriched the pathogenesis of diabetes, and it perhaps will provide new ideas for the prevention and treatment of T2DM.

内毒素血症可导致T2DM的发生，内毒素的主要成份脂多糖（LPS）可通过调控RACK1/NF-KB通路而诱导加剧胰岛β细胞过度自噬而引发T2DM。但通过减缓胰岛β细胞过度自噬来改善LPS诱导的T2DM研究尚未见报道。课题组前期研究发现黄芪多糖可抑制LPS刺激条件下胰岛β细胞LC3-I的表达，并可抑制T2DM大鼠NF-KB的表达，但其具体机制不明。我们进一步预实验发现黄芪多糖可上调LPS刺激条件下胰岛β细胞RACK1的表达。因此我们猜想黄芪多糖可通过调控RACK1/NF-KB通路阻断LPS诱导的胰岛β细胞过度自噬而减缓T2DM。本课题将采用LPS诱导构建的T2DM大鼠模型以及基因过表达、microRNA的靶基因验证等分子生物学技术，探讨黄芪多糖缓解LPS诱导的T2DM的分子机制。其结果可进一步丰富糖尿病的发病机制，并可能为T2DM的防治提供新思路。

内毒素血症可导致T2DM的发生。内毒素的主要成份脂多糖（LPS）可通过调控RACK1/NF-KB通路而诱导加剧胰岛β细胞过度自噬而引发T2DM。本项目按照原计划研究了黄芪多糖对LPS诱导的胰岛β细胞RACK1、NF-KB、LC3-I等自噬因子的变化，发现黄芪多糖确实可以阻断LPS诱导的RACK1下调，缓解β细胞自噬，但对胰岛β细胞NF-KB表达则无抑制作用。经过转录组测序研究后探讨了Akt/mTOR信号通路，发现黄芪多糖可以通过激活Akt/mTOR通路抑制胰岛β细胞自噬，改善LPS诱导的T2DM。基本阐明了黄芪多糖缓解LPS诱导的T2DM的分子机制，该结果可进一步丰富糖尿病的发病机制，并可能为T2DM的防治提供新的思路。