p38 MAPK抑制剂SB203580减轻罗哌卡因对PC12细胞的毒性  

P38 MAPK inhibitor SB203580 attenuates the toxicity of ropivacaine on PC12 cells

作　　者：陈园 王锷[1] 孙志华 宋宗斌[1] 叶治[1] 张重[1] CHEN Yuan;WANG E;SUN Zhihua;SONG Zongbin;YE Zhi;ZHANG Zhong(Department of Anesthesiology,Xiangya Hospital,Central South University,Changsha 410008;Department of Anesthesiology,Xiangya Changde Hospital,Changde Hunan 415000,China)

机构地区：[1]中南大学湘雅医院麻醉科,长沙410008 [2]湘雅常德医院麻醉科,湖南常德415000

出　　处：《中南大学学报（医学版）》2019年第9期985-989,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81301043)~~

摘　　要：目的:探讨p38MAPK抑制剂SB203580对罗哌卡因诱发大鼠肾上腺嗜铬细胞瘤细胞(PC12)的毒性的影响及其机制。方法:将PC12细胞分为对照组(N组)、罗哌卡因组(R组,15mmol/L盐酸罗哌卡因)、罗哌卡因+SB203580组(R+S组,15mmol/L盐酸罗哌卡因+10μmol/LSB203580)。培养48h后行3组细胞计数并采用MTT法检测细胞存活率;采用蛋白质印迹法检测各组磷酸化p38(p-p38)、活化的caspase-3的表达以及细胞质中细胞色素C(cytochromeC,CytC)的含量。结果:与N组比较,R组和R+S组的PC12细胞数目及细胞存活率均显著减少(均P<0.05);且R+S组的PC12细胞数目和存活率较R组显著上升(均P<0.05)。与N组比较,R组和R+S组p-p38,活化的caspase-3的表达以及细胞质中CytC的含量显著增加(均P<0.05);与R组比较,R+S组p-p38,活化的caspase-3的表达以及细胞质中CytC的含量明显减少(均P<0.05)。结论:抑制p38磷酸化可减轻罗哌卡因对PC12细胞的毒性作用,其机制可能与减少释放入细胞质的CytC和caspase-3的活化有关。Objective:To investigate the effect of SB203580,a p38MAPK specific inhibitor,on ropivacaineinduced cytotoxicity in PC12 cells. Methods:PC12 cells were divided into three groups:the normal group (Group N),cells were cultured for 48 h;the ropivacaine group (Group R),cells were cultured with 15 mmol/L ropivacaine hydrochloride for 48 h;the ropivacaine+SB203580 group (Group R+S),cells were cultured with 15 mmol/L ropivacaine hydrochloride plus 10 μmol/L SB203580 for 48 h.The cell survival rates were detected by MTT assay.The protein levels of cleaved caspase-3,phosphor-p38(p-p38) and cystolic cytochrome C (Cyt C) were detected by Western blotting. Results:Compared with the Group N,the number and survival rate of PC12 cells in the Group R and the Group R+S were significantly reduced (all P<0.05);the number and survival rate of PC12 cells in the Group R+S were significantly higher than those in the Group R (both P<0.05). Compared with the Group N,the levels of p-p38 and cleaved caspase-3,and the content of cytoplasmic Cyt C in the PC12 cells from the Group R and the Group R+S were significantly enhanced (all P<0.05);compared with the Group R,the levels of p-p38 and cleaved caspase-3, and the content of cytoplasmic Cyt C in the PC12 cells from the Group R+S were decreased (all P<0.05). Conclusion:The ropivacaine-induced cytotoxicity can be attenuated via inhibition of p38MAPK;which is related to decrease in Cyt C content and cleaved caspase-3 expression.

关 键 词：罗哌卡因 毒性 p38MAPK SB203580 PC12细胞 细胞色素C caspase-3 

分 类 号：R965[医药卫生—药理学]