sKlotho 通过调控 RIP1 的表达对缺血性脑卒中的改善作用
摘要
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。
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[1]. Cho, S.M., et al., Risk Factors of Ischemic and
Hemorrhagic Strokes During Venovenous Extracorporeal
Membrane Oxygenation: Analysis of Data From the Extracorporeal
Life Support Organization Registry. Crit Care Med, 2021. 49（1）:
p. 91-101.
[2]. Martins, I.J., Anti-Aging Genes Improve Appetite
Regulation and Reverse Cell Senescence and Apoptosis in Global
Populations. Advances in Aging Research, 2018. 05（01）: p. 9-26.
[3]. Goossens, V., et al., Direct evidence for tumor necrosis
factor-induced mitochondrial reactive oxygen intermediates and
their involvement in cytotoxicity. Proc Natl Acad Sci U S A, 1995.
92（18）: p. 8115-9.
[4]. Dowling, J.P., et al., Kinase-independent function of
RIP1, critical for mature T-cell survival and proliferation. Cell
Death Dis, 2018. 7（9）: p. e2379.
[5]. Nikseresht, S., F. Khodagholi, and A. Ahmadiani,
Protective effects of ex-527 on cerebral ischemia-reperfusion
injury through necroptosis signaling pathway attenuation. J Cell
Physiol, 2020. 234（2）: p. 1816-1826.
[6]. Linkermann, A., et al., Necroptosis in immunity and
ischemia-reperfusion injury. Am J Transplant, 2015. 13（11）: p.
2797-804.
[7]. Blackwell, K., et al., Two coordinated mechanisms
underlie tumor necrosis factor alpha-induced immediate and
delayed IkappaB kinase activation. Mol Cell Biol, 2020. 33（10）:
p. 1901-15.
[8]. Zemirli, N., et al., The E3 ubiquitin ligase RNF121 is a
positive regulator of NF-kappaB activation. Cell Commun Signal,
2019. 12: p. 72.
[9]. Ando, K., et al., PIDD death-domain phosphorylation by
ATM controls prodeath versus prosurvival PIDDosome signaling.
Mol Cell, 2012. 47（5）: p. 681-93.
[10]. Upton, J.W., W.J. Kaiser, and E.S. Mocarski, DAI/
ZBP1/DLM-1 Complexes with RIP3 to Mediate Virus-Induced
Programmed Necrosis that Is Targeted by Murine Cytomegalovirus
vIRA. Cell Host Microbe, 2021. 26（4）: p. 564.
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