瑞舒伐他汀通过UCP2-SIRT3信号调控脑I/R对神经元的损伤  

Rosuvastatin regulates cerebral I/R damage to neurons by UCP2-SIRT3 signal

作　　者：云强 董雪佳 王梦娇 刘雅虹 王智光[3] 江名芳[3] YUN Qiang;DONG Xuejia;WANG Mengjiao;LIU Yahong;WANG Zhiguang;JIANG Mingfang(Department of Neurosurgery,People's Hospital of Inner Mongolia Autonomous Region,Hohhot 010020,Inner Mongolia,China;Graduate School of Inner Mongolia Medical University,Hohhot 010058,Inner Mongolia,China;Department of Neurology,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010059,Inner Mongolia,China)

机构地区：[1]内蒙古自治区人民医院神经外科,内蒙古呼和浩特市010020 [2]内蒙古医科大学研究生院,内蒙古呼和浩特市010058 [3]内蒙古医科大学附属医院神经内科,内蒙古呼和浩特市010059

出　　处：《中国临床药理学与治疗学》2021年第2期144-153,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：内蒙古自治区科技计划项目(201702144);内蒙古医科大学附属医院博士启动金项目(NYFY BS 2018);内蒙古自然科学基金面上项目(2020MS08197);内蒙古自治区自然科学基金项目(2018LH08012)。

摘　　要：目的:研究瑞舒伐他汀对脑缺血-再灌注损伤的保护作用及作用机制。方法:(1)建立脑梗死及OGD/R细胞模型,检测不同浓度瑞舒伐他汀对细胞增殖及细胞凋亡的影响;(2)用不同浓度瑞舒伐他汀处理OGD/R细胞模型,观察瑞舒伐他汀对细胞形态和细胞中UCP2/SIRT3表达和定位的影响;(3)构建UCP2沉默的细胞系,观察细胞线粒体形态和细胞中TOMM20及SIRT3分子表达与定位,研究瑞舒伐他汀在OGD/R细胞模型中发挥保护作用的通道和机制;(4)检测线粒体膜电位,PCR检测线粒体生成基因PGC1、Drp1和Opa1表达,研究瑞舒伐他汀对线粒体的保护作用。结果:(1)不同浓度瑞舒伐他汀均可以明显减低OGD/R细胞凋亡,提高细胞存活率;(2)瑞舒伐他汀通过影响细胞UCP2和SIRT3表达,进而发挥细胞保护作用,使细胞免受OGD/R损伤;(3)瑞舒伐他汀通过调控UCP2影响TOMM20表达,增加线粒体跨膜转运和能量代谢,增强线粒体功能,提高细胞存活;(4)瑞舒伐他汀阻止OGD/R细胞膜电位下降,保护线粒体,改善细胞状态,减少细胞凋亡。结论:瑞舒伐他汀通过调控UCP2/SIRT通路来抑制OGD/R细胞线粒体损伤,从而发挥神经元保护作用。AIM:To study the protective effect and mechanism of rosuvastatin on cerebral ischemia-reperfusion injury.METHODS:(1)Cerebral infarction and OGD/R cell models were established to detect the effects of different concentrations of rosuvastatin on cell proliferation and apoptosis;(2)Different concentrations of rosuvastatin were used to treat OGD/R cell models and to observe rosuvastatin effects on cell morphology and expression and localization of UCP2-SIRT3 in cells;(3)UCP2 silent cell line was constructed to observe cell mitochondrial morphology and expression and localization of TOMM20 and SIRT3 molecules in cells,and to study the channels and mechanisms that play a protective role of rosuvastatin in OGD/R cell model;(4)The mitochondrial membrane potential,mitochondrial gene PGC1,Drp1 and Opa1 expression were detected to study the protective effect of rosuvastatin on mitochondria.RESULTS:(1)Rosuvastatin of different concentrations could significantly reduce OGD/R cell apoptosis and increase cell survival rate;(2)Rosuvastatin exerted cell protection by affecting the expression of UCP2 and SIRT3 in cells,thereby protecting cells from OGD/R injury;(3)Rosuvastatin affected the expression of TOMM20 by regulating UCP2,increased mitochondrial transmembrane transport and energy metabolism,enhanced mitochondrial function,and improved cell state and reduced apoptosis.CONCLUSION:Rosuvastatin inhibits mitochondrial damage of OGD/R cells by regulating UCP2/SIRT pathway,thereby exerting neuron protection.

关 键 词：瑞舒伐他汀 UCP2 SIRT3 OGD/R 缺血再灌注 

分 类 号：R965.2[医药卫生—药理学]