RHO/ROCK信号通路抑制剂在奥沙利铂化疗施旺细胞损伤中的保护作用研究  

Protective effect of RHO/ROCK signaling pathway inhibitor on SCs oxaliplatin chemotherapy injury

作　　者：李娜[1] 姚娜 田稼[2] LI Na;YAO Na;TIAN Jia(Department of Neuroelectrophysiology,People's Hospital of Ningxia Hui Autonomous Region,Yinchuan 750002,China;Surgery Department,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏回族自治区人民医院神经电生理科,宁夏银川750002 [2]宁夏医科大学总医院外科,宁夏银川750004

出　　处：《宁夏医学杂志》2022年第1期26-28,I0001,共4页Ningxia Medical Journal

基　　金：宁夏青年科技人才托举工程项目(2016158)。

摘　　要：目的明确RHO/ROCK信号通路抑制剂在化疗致施旺细胞(SCs)损伤中的保护作用及化疗所致的周围神经病变(CIPN)预防中的价值。方法将SCs分为对照组、实验组及抑制剂组,实验组加入奥沙利铂(0.5 mol/mL),抑制剂组细胞加入RHO/ROCK信号通路抑制剂Y27632(10μmol/mL)2 h后加入奥沙利铂;CCK8检测3组细胞增殖状况;流式细胞仪检测SCs凋亡率及细胞线粒体膜电位(MMP)变化;Western blot检测SCs凋亡及线粒体结构功能相关蛋白表达。结果与正常对照组比较,实验组细胞凋亡率增加而细胞MMP下降,Western blot检测实验组细胞Bcl2、OPA1和TOM70蛋白表达下调,而Bax、Caspase3及DRP1蛋白表达上调;抑制剂组与实验组比较细胞凋亡率下降,MMP升高,Bcl2、OPA1及TOM70蛋白表达上调,Bax、Caspase3及DRP1蛋白表达下调。结论RHO/ROCK通路抑制剂通过保护SCs线粒体功能及结构完整性,抑制奥沙利铂诱导的SCs细胞凋亡,RHO/ROCK通路抑制剂在CIPN预防治疗中具有潜在应用价值。Objective To clarify the protective effect of RHO/ROCK signaling pathway inhibitors on chemotherapy-induced Schwann cell(SCs)injury and the value of chemotherapy-induced peripheral neuropathy(CIPN)prevention.Methods SCs were divided into control group,experimental group and inhibitor group.The experimental group was added with oxaliplatin(0.5 mol/mL),and the inhibitor group was added with RHO/ROCK signaling pathway inhibitor Y27632(10 mol/mL).After two hours,0.5 mol/ml oxaliplatin was added;CCK8 was used to detect cell proliferation among three groups;flow cytometry was used to detect the apoptosis rate of SCs and cell mitochondrial membrane potential(MMP)changes;western blot was used to detect the apoptosis and mitochondrial structure of SCs function-related protein expression.Results Compared with the normal control group,the apoptosis rate of the experimental group was increased,while the cell MMP was decreased.Western blot showed that the expression of Bcl2,OPA1 and TOM70 protein in the experimental group was down-regulated,while the expression of Bax,Caspase3 and DRP1 protein was up-regulated.Compared with the experimental group,the rate of apoptosis,Bax,Caspase3 and DRP1 protein expression were decreased,while the Bcl2,OPA1 and TOM70 protein expression was increased in the inhibitor group.Conclusion RHO/ROCK pathway inhibitors can protect SCs mitochondrial function and structural integrity,and inhibit oxaliplatin-induced apoptosis of SCs.RHO/ROCK pathway inhibitors have potential application value in the prevention and treatment of CIPN.

关 键 词：RHO/ROCK信号通路 抑制剂 化疗所致的周围神经病变 施旺细胞 

分 类 号：R745[医药卫生—神经病学与精神病学]