Effects of N-n-butyl haloperidol iodide on rat myocardial ischemia and reperfusion injury and L-type calcium current  

N-正丁基氟哌啶醇碘化物对大鼠心肌缺血再灌注损伤及L-型钙电流的影响(英文)

作　　者：黄展勤[1] 石刚刚 郑锦鸿 刘冰 

机构地区：[1]汕头大学医学院药物研究室 [2]鲁尔大学生理学教研室

出　　处：《Acta Pharmacologica Sinica》2003年第8期31-37,111,共7页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (№ 30070304);the National New Drug Research Foundation of China (№ 9690105231);the Foundation of Scientific and Technologic Project of Guangdong province of China (№ C30104);the

摘　　要：AIM: To study the effects of N-n-butyl haloperidol iodide （F₂） on rat heart ischemia/reperfusion （I/R） injury and L-type calcium current (I_Ca) in rat ventricular myocytes. METHODS: Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring perfusion for 30 min. F₂ （1, 2, and 4 mg/kg） were iv injected before ischemia. Plasma creatine kinase （CK）, creatine kinase isoenzyme MB （CK-MB）, lactate dehydrogenase （LDH）, α-hydroxybutyrate dehydrogenase （HBDH）, glutamic-oxaloacetic transaminase （GOT）, malondialdehyde （MDA） concentrations, and superoxide dismutase （SOD） activity were measured. The pathologic changes of I/R myocardium were assessed by the transmission electron microscopy. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique. RESULTS: F₂ reduced the release of CK, CK-MB, LDH, HBDH and GOT, preserved the activity of SOD, and decreased the MDA contents dose-dependently. For morphology, F₂ mollified the pathologic changes of myocardium induced by I/R injury. F₂ 1 μmol/L decreased I_Ca from （1775±360） pA to （464±129） pA （n=8, P【0.01） and shifted the current-voltage of I_Ca upward, without affecting the voltage-dependent properties of I_Ca. CONCLUSION: F₂ played a protective role against rat heart I/R injury in a dose-dependent manner, and inhibited I_Ca in rat ventricular myocytes. The cardioprotective and vasodilatory mechanisms of F₂ may be related to its inhibitory effect on L-type calcium channel.目的:观察N-正丁基氟哌啶醇碘化物(F_2)对大鼠心肌缺血再灌注损伤及大鼠心室肌细胞L-型钙电流(I_(Ca))的影响。方法:大鼠冠脉左前降支结扎30 min后恢复灌注30 min,于缺血前分别静脉注射F_2(1,2,和4 mg/kg)。测定血浆CK、CK-MB、LDH、HBDH、GOT、MDA的含量及SOD活性;观察心肌的形态学改变。采用酶急性分离的大鼠单个心室肌细胞,应用膜片箝全细胞记录技术,观察F_2对I_(Ca)的影响。结果:F_2呈量效依赖地降低缺血再灌注心肌酶CK、CK-MB、LDH、HBDH、GOT的释放,保护SOD的活性,降低MDA的产生;电镜下可见F_2减轻心肌的形态学改变。F_2 1 μmol/L明显抑制I_(Ca),使峰电流从(1775±360)pA减少至(464±129)pA(n=8,P<0.01),并使得I_(Ca)的I-V曲线上移,但不改变其电压依赖特征。结论:F_2对大鼠心肌缺血再灌注损伤具有拮抗作用,并可抑制大鼠心室肌细胞L-型钙电流。F_2对心肌缺血再灌注损伤的拮抗作用及其扩张血管的机制可能与其阻断L-型钙通道有关。

关 键 词：HALOPERIDOL ischemia-reperfusion injury MYOCARDIUM L-type calcium channels electron microscopy patch-clamp techniques 

分 类 号：R96[医药卫生—药理学]