sKlotho 通过调控 RIP1 的表达对缺血性脑卒中的改善作用
摘要
目的：探讨 sKlotho 通过调控 RIP1 的表达对缺血性脑卒中的改善作用，从新的视角深入了解缺血性脑卒中后 sKlotho 的变化规律及作用，阐明 sKlotho 参与缺血性脑卒中后 RIP1 表达调控的分子机制，对深化缺血性脑卒中的病理过程 理解和设定临床干预靶点奠定基础。方法：。将健康雄性 C57BL/6 鼠 40 只，随机平均分为对照组（Sham）、模型组（MCAO）。 采用 Real-time PCR、Western blotting、免疫组化染色等方法检测 sKlotho、RIP1 蛋白和 mRNA 的表达变化；采用 Co-IP 方法检测 sKlotho 和 RIP1 蛋白的相互作用。结果： Klotho 在 MCAO 模型小鼠脑部水平降低（P ＜ 0.05），过表达 Klotho 能有效抑制神经元死亡并缓解脑损伤和神经功能障碍。MCAO 模型神经元呈现坏死性凋亡蛋白 RIP1 和 MLKL 激活等坏死 性凋亡改变，过表达 Klotho 促进 RIP1 降解（P ＜ 0.05），并减轻了神经元坏死性凋亡。结论：Klotho 促进 RIP1 降解、抑 制神经元坏死性凋亡可能是其脑卒中后脑保护作用的重要方式。参考
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