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钙敏感受体在帕金森病发病中的机制研究

陈 曦, 许 叶, 王 埮
海南医学院第一附属医院

摘要


目的:探讨钙敏感受体(CaSR)抑制剂(Calhex231)、CaSR激动剂(GdCl3)对PD炎症细胞模型发挥的作用。研究能否通过调控CaSR来影响的PD发生发展,为PD的研究提供了新的思路。方法:使用MPP+在人神经母细胞瘤(SH-SY5Y)细胞上制备PD炎症细胞模型,使用CCK8法检测不同浓度MPP+、Calhex231、GdCl3处理后对SH-SY5Y细胞增殖的影响,确定合适的药物实验浓度。分为空白对照组、MPP+组、Calhex231组、GdCl3组、MPP++Calhex231组、MPP++GdCl3组。采用Westernblot法检测各分组中CaSR、TH蛋白的表达水平和灰度分析;采用PCR法检测各分组中CaSR的mRNA表达水平;采用CCK8法分别检测各组细胞增殖的情况。结果:与空白对照组相比,使用250μmol/L的MPP+、25μmol/L的GdCl3处理后能明显抑制细胞增殖,使用3.13μmol/LCalhex231处理后可明显促进细胞增殖;与空白对照组比较,MPP+组、GdCl3组TH蛋白表达含量降低,Calhex231组TH蛋白表达含量升高;与MPP+组比较,MPP++Calhex231组TH蛋白表达含量升高,MPP++GdCl3组TH蛋白表达含量降低;与空白对照组相比,MPP+组、GdCl3组中CaSR的mRNA及CaSR蛋白表达上调,Calhex231组中CaSR的mRNA及CaSR蛋白表达下降;与MPP+组相比,MPP++Calhex231组中的CaSR的mRNA及CaSR蛋白表达下降、MPP++GdCl3组中CaSR的mRNA及CaSR蛋白表达上调;与空白对照组比较,MPP+、GdCl3组细胞增殖被抑制,Calhex231组细胞增殖被激活,与MPP+组相比,MPP++GdCl3组细胞增殖被抑制,MPP++Calhex231组细胞增殖被激活。结论CaSR抑制剂可促进PD炎症细胞模型增殖,CaSR调节剂可影响PD发生、发展过程。

关键词


钙敏感受体;帕金森病;神经母细胞瘤细胞;神经炎症;NLRP3

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参考


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DOI: http://dx.doi.org/10.12361/2661-3603-05-10-132048

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