碘化N-正丁基氟哌啶醇通过非外钙机制抗心肌细胞缺氧复氧损伤  

N-n-butyl haloperidol iodide protects cardiomyocytes against hypoxia/reoxygenation injury through an extracellular calcium-independent mechanism

作　　者：张艳美[1] 陈高勇[1] 李伟秋[2] 徐涵[1] 郑燕珊[1] 刘幸平[1] 郑付春[3] 

机构地区：[1]汕头大学医学院药理教研室,515041 [2]汕头大学医学院分析细胞实验室,515041 [3]汕头大学医学院第一附属医院药剂科

出　　处：《中国药物与临床》2013年第6期689-691,共3页Chinese Remedies & Clinics

基　　金：国家自然科学基金(81072633);国家自然科学基金-广东省自然科学基金联合资助基金(U0932005)

摘　　要：目的研究碘化N-正丁基氟哌啶醇(F2)对大鼠心肌细胞无外钙缺氧/复氧(H/R)损伤的作用及其机制。方法建立无外钙(零钙液)的心肌细胞H/R模型,于缺氧液及复氧液中加入1×10-6mol/L的F2。倒置显微镜下观察细胞形态结构及搏动的变化;采用蛋白印迹法检测心肌细胞磷酸化ERK(p-ERK1/2)、总ERK1/2蛋白表达的变化。结果零钙液H/R可引起培养心肌细胞形态结构呈损伤性改变,包括胞体收缩、伪足减少和搏动无力;零钙液H/R可引起培养心肌细胞p-ERK1/2表达增加,但不影响总ERK表达,即可激活培养心肌细胞ERK1/2;F2可以改善零钙液H/R状态下心肌细胞形态结构的损伤。F2对零钙液H/R心肌细胞p-ERK1/2高表达具有抑制作用,但不影响总ERK的表达。结论 F2可通过非外钙依赖机制拮抗心肌细胞H/R损伤,这可能与其抑制零钙液H/R状态下ERK1/2的激活密切相关。Objective To investigate the effect of N-n-butyl haloperidol iodide （F2） on hypoxia/reoxygenation （H/R） injury to cardiomyocytes cultured in extracellular-Ca2＋-free medium and its mechanism. Methods The H/R models of neonatal rat cardiomyocytes in extraceilular-Ca2＋-free （Ca2＋-free） medium were established. Changes in morphology and spontaneous beat of the cardiomyocytes were detected by inverted microscopy. Expressions of p-ERK1/2 and total ERK protein were examined by western-blot analyses. Results H/R caused damage to the cardiomycytes in Ca2＋-free medium including cell shrinkage, pseudopod reduction and beat weakness. The expression level of p-ERK1/2, rather than that of total ERK, increased in the cardiomyocytes when subjected to H/R with Ca2＋-free medium, indicating ERK1/2 became activated after H/R. Treatment with F2 during hypoxia and reoxygenation significantly attenuated the cardiomyocytes＇ injury in Ca2＋-free medium and inhibited the overexpression of p-ERK but not the expression of total ERK. Conclusion F2 can protect cardiomyocytes against H/R-induced injury through a calcium-independent mechanism, which might be closely related to the inhibition effect of F2 on activation of ERK1/2 induced by Ca2＋-free- H/R.

关 键 词：氟哌啶醇 心肌细胞 缺氧 复氧 损伤 

分 类 号：R96[医药卫生—药理学]