基于miR-140-3p/SIRT1信号轴探讨山药多糖防治妊娠糖尿病的分子机制

Gestational diabetes mellitus (GDM) has a serious impact on the health of mother and infant. However, with the special onset period and complex pathogenesis, its treatment is also limited as well. We firstly discovered that miR-140-3p is close related to GDM and Yam polysaccharide effect notable on the prevention and treatment GDM by regulating the expression of miR-140-3p. And it has been.confirmed that the target gene SIRT1 of miR-140-3p is a key joint in the regulation of insulin resistance. So our hypothesis is the prevention and treatment of Yam polysaccharide on GDM may be effected by the adjustment of miR-140-3p /SIRT1 signal shaft. In order to verify this hypothesis, we plan to apply the experiments of in vivo and vitro with a GDM mice model and an insulin resistance cell model respectively in this study, and detect the changes of insulin resistance and other relevant indications of SIRT1-FOXO1/PGC-1α/NF-kB signal shaft by the overexpression/over suppression miR-140-3p and SIRT1 individually or commonly before and after the intervention of Yam polysaccharide.in these models, and finally to illuminate the molecular mechanism of miR-140-3p on regulation of insulin resistance in GDM and the effective mechanism of and Yam polysaccharide in it. Those work are not only beneficial to deeply understand the.pathogenesis of GDM, but also lay foundation of the safety, effective and convenient drug development in the future.

妊娠期糖尿病（GDM）严重影响母婴的健康。然而，GDM发生时期特殊、发病机制复杂、治疗手段有限。我们首次发现miR-140-3p与GDM密切相关，而山药多糖防治GDM效果显著，且调节miR-140-3p表达。现已明确，其靶基因SIRT1是调节胰岛素抵抗的关键节点。因此，推测山药多糖可能通过调节miR-140-3p/SIRT1信号轴以发挥疗效。为了验证该假说，本项目拟采用体内结合体外实验方法，应用GDM小鼠模型和胰岛素抵抗细胞模型，利用慢病毒基因转染，过表达或抑制miR-140-3p、SIRT1，或给予山药多糖处理，检测胰岛素抵抗、SIRT1-FOXO1/PGC-1α/NF-kB信号轴等相关指标变化，以阐明miR-140-3p调节GDM胰岛素抵抗的分子机制，同时明确山药多糖防治GDM的作用机制。这不仅有利于深入理解GDM的发生机制，还将为临床应用提供依据。

妊娠期糖尿病（GDM）严重影响母婴的健康。我们首次发现miR-140-3p与GDM密切相关，而山药多糖防治GDM效果显著，且调节miR-140-3p表达。现已明确，其靶基因SIRT1是调节胰岛素抵抗的关键节点。因此，推测山药多糖可能通过调节miR-140-3p/SIRT1信号轴以发挥疗效。为了验证该假说，本项目应用GDM小鼠模型和胰岛素抵抗细胞模型，利用慢病毒基因转染，过表达或抑制miR-140-3p、SIRT1，或给予山药多糖处理，检测胰岛素抵抗、SIRT1-FOXO1/PGC-1α/NF-kB信号轴等相关指标变化，发现观察小鼠空腹血糖、空腹血清胰岛素、胰岛素抵抗指数、口服葡萄糖耐量试验、胰岛素耐量试验等相关指标均较对照组显著性升高，小鼠肝脏组织SIRT1-FOXO1/PGC-1α/NF-ΚB信号轴相关基因和蛋白活性显著性降低，明确miR-140-3p促进妊娠糖尿病中的作用。同时发现山药多糖可以抑制胰岛素抵抗指标及SIRT1-FOXO1/PGC-1Α/NF-ΚB信号轴相关基因表达水平和蛋白活性。