sKlotho 通过调控 RIP1 的表达对缺血性脑卒中的改善作用

  • 石 雨妍 西安培华学院
  • 魏  璇 西安培华学院
  • 张 思怡 西安培华学院
  • 曹 欣瑶 西安培华学院
  • 毕 芳芳 西安培华学院
关键词: sKlotho;RIP1;缺血性脑卒中


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。


[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.


[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.


[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.


[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.