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Research Article

TRPM 7在内毒素血症中的表达抑制和活性抑制对细胞因子产生和多器官功能障碍综合征的调节作用：脓毒症的新靶点

卷 19, 期 8, 2019

页: [547 - 559] 页: 13

弟呕挨: 10.2174/1566524019666190709181726

摘要

背景：脓毒症和内毒素血症期间检测到的主要病理特征包括促炎细胞因子的过度分泌和多器官功能障碍综合征（MODS）。不幸的是，目前临床治疗脓毒症的努力不能令人满意，死亡率仍然很高。 有趣的是 瞬时受体电位(Trp)美司他丁7(TRPM 7)离子通道控制Ca2+和Mg2+通透性参与细胞因子的产生和炎症反应。此外，在某些脓毒症模型中，TRPM 7的下调已被证明可以减轻局部症状，但其在系统水平上的影响仍有待探讨。 目的：探讨TRPM 7是否介导内毒素血症时细胞因子的产生和MODS的发生。 方法：对内毒素性和假内毒素性大鼠采用卡伐罗尔对TRPM 7进行药理抑制，或用腺病毒载体shRNA(AdVshTRPM 7)抑制TRPM 7的表达。然后, 测定血液中细胞因子和多器官功能紊乱综合征(MODS)水平。 结果: 用香芹酚抑制TRPM7并用AdVshTRPM7抑制均能有效抑制内毒素血症大鼠促炎细胞因子TNF-α，IL-1β，IL-6和IL-12的过度分泌，而不会诱导血液水平中抗炎细胞因子IL-10和IL-4下调。此外，使用香芹酚和AdVshTRPM7可显着预防由内毒素血症引起的肝脏和胰腺功能障碍，代谢功能改变和低血糖症。 此外，在内毒素血症大鼠中使用香芹酚和AdVshTRPM7也显着降低了肌肉萎缩和心肌损伤。 结论：TRPM 7离子通道是脓毒症中调节炎症反应和MODS的关键蛋白。此外，TRPM 7被认为是一种治疗脓毒症的新的分子靶点。

关键词: 内毒素血症，TRPM 7，细胞因子，脓毒症，器官功能障碍，多器官功能紊乱综合征。

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