碘化N-正丁基氟哌啶醇通过抑制线粒体凋亡通路抗H9c2心肌细胞缺氧/复氧损伤  

N-n-butyl haloperidol iodide protects H9c2 cardiac myocytes against hypoxia/reoxygenation injury through mitochondria-dependent apoptotic pathway

作　　者：汪彬[1] 黄丹梅[1] 王远航[1] 周巧玲[1] 林泓[1] 张艳美[1] 石刚刚[1] 郑付春[2] 

机构地区：[1]汕头大学医学院药理学教研室,广东汕头515041 [2]汕头大学医学院第一附属医院药剂科,广东汕头515041

出　　处：《中国药理学通报》2017年第6期819-823,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金-广东省自然科学基金联合资助基金项目(No U0932005);广东省科技厅公益研究与能力建设专项资金项目(No 2014A020212290);国家自然科学基金资助项目(No 81473215)

摘　　要：目的研究碘化N-正丁基氟哌啶醇(F2)对H9c2心肌细胞缺氧/复氧(H/R)损伤中线粒体凋亡通路的影响,并探讨其分子作用机制。方法建立H9c2心肌细胞H/R损伤模型,将H9c2心肌细胞随机分为5组:正常对照组(C组)、缺氧/复氧组(H/R组)、F_2低、中、高剂量组。流式细胞术分析测定细胞凋亡率;采用蛋白免疫印迹(Western blot)检测细胞色素C(Cyto C)、Bcl-2、和Bax蛋白表达变化;比色法测定caspase-3的活性。结果与H/R组相比,F_2低、中、高剂量组可明显降低H9c2细胞缺氧/复氧损伤后细胞凋亡率;提高Bcl-2/Bax比值;抑制线粒体中Cyto C的释放;减少caspase-3的活性。结论 F_2能够降低H/R后H9c2心肌细胞凋亡率,其机制可能与抑制线粒体通路的细胞凋亡有关。Aim To investigate the effect of N-n-butyl haloperidol iodide( F_2) on mitochondria-dependent apoptotic pathway of H9c2 cardiac myocytes during hypoxia/reoxygenation( H/R) injury. Methods The H/R models of H9c2 cardiac myocytes were established.The H9c2 cardiac myocytes were randomly divided into five groups: control group( C group),hypoxia/reoxygenation group( H/R group), F_2 low concentration group( L),F_2 medium concentration group( M),F_2 high concentration group( H). Apoptotic rate was evaluated by flow cytometry( FCM). The levels of Cyto C,Bcl-2,Bax were observed by Western blot. Caspase-3 activity was measured with colorimetry. Results Compared with H/R group,F_2 low,medium and high concentrations group could significantly decrease apoptosis rate and increase the ratio of Bcl-2 to Bax proteins and inhibit the release of Cyto C into the cytosolic fraction,and decrease caspase-3 activity. Conclusion F_2 can protect H9c2 cardiac myocytes against H/R-induced injury through interfering in mitochondria-dependent pathway.

关 键 词：碘化N-正丁基氟哌啶醇 缺氧/复氧 H9C2心肌细胞 凋亡 线粒体 细胞色素C 

分 类 号：R322.11[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]