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氟哌啶醇季铵盐衍生物对大鼠心肌缺血再灌注损伤保护作用的研究
引用本文:黄展勤,石刚刚,陈彩云,李伟秋,吴惜贞,刘幸平. 氟哌啶醇季铵盐衍生物对大鼠心肌缺血再灌注损伤保护作用的研究[J]. 中国药理学通报, 2002, 18(3): 298-302
作者姓名:黄展勤  石刚刚  陈彩云  李伟秋  吴惜贞  刘幸平
作者单位:汕头大学医学院药物研究室,汕头,515031
基金项目:国家自然科学基金 (No 3 0 0 70 3 0 4),国家新药研究基金 (No 96 90 1 0 5 2 3 ),广东省自然科学基金(No 970 60 5 )资助课题
摘    要:目的 研究氟哌啶醇季铵盐衍生物 (F2 )对大鼠心肌缺血再灌注损伤的影响。方法 大鼠冠状动脉左前降支结扎 30min ,再灌注 30min ,于缺血前舌下静脉注射不同剂量F2 (1,2 ,4mg·kg-1)。测定血清肌酸激酶 (CK)、肌酸激酶同工酶MB (CK MB)、乳酸脱氢酶 (LDH)、α 羟丁酸脱氢酶(HBDH)、谷草转氨酶 (GOT)、丙二醛 (MDA)的含量 ,超氧化物歧化酶 (SOD)活性 ;透视电子显微镜下观察心肌形态学改变。结果 F2 能呈量效关系降低由于缺血再灌注引起的心肌损害心肌酶CK、CK MB、LDH、HBDH、GOT的释放 ,保护SOD的活性 ,降低MDA的产生 ;透视电子显微镜下可观察到F2 能减轻缺血再灌注心肌的形态学改变。结论 F2 对大鼠心肌缺血再灌注损伤具有保护作用

关 键 词:氟哌啶醇季铵盐  心肌缺血再灌注损伤  肌酸激酶同工酶MB  超氧化物歧化酶  丙二醛  电子显微镜
文章编号:1001-1978(2002)03-0298-05

Protective effects of quateranary ammonium salt derivative (F2) of haloperidol on ischemia and reperfusion injury in rat hearts
HUANG Zhan Qin,SHI Gang Gang,CHEN Cai Yun,LI Wei Qiu,WU Xi Zheng,LIU Xing Ping. Protective effects of quateranary ammonium salt derivative (F2) of haloperidol on ischemia and reperfusion injury in rat hearts[J]. Chinese Pharmacological Bulletin, 2002, 18(3): 298-302
Authors:HUANG Zhan Qin  SHI Gang Gang  CHEN Cai Yun  LI Wei Qiu  WU Xi Zheng  LIU Xing Ping
Abstract:AIM To study the effects of quateranary ammonium salt derivative (F 2) of haloperidol on ischemia and reperfusion injury in rat hearts. METHODS Ischemia and reperfusion injury in rat hearts was induced by occluding the left anterior descending coronary artery for 30 min and restoring blood reperfusion for 30 min. F 2 (1, 2, 4 mg·kg -1 , respectively) was intravenously injected before heart ischemia. Plasma creatine kinase (CK), creatine kinase isoenzyme MB(CK MB), lactate dehydrogenase(LDH),α Hydroxybutyrate dehydrogenase (HBDH), grutamic oxalacetic transaminase(GOT), superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were measured. The pathologic changes of ischemia and reperfusion myocardium were observed on the transmission electron microscopy. RESULTS F 2 reduced the release of CK,CK MB LDH,HBDH,GOT from I/R rat hearts, increased the activity of SOD and decreased the MDA contents. In F 2 (1mg·kg -1 ) group, the serum CK MB LDH HBDH concentration was lowered significantly (vs I/R group P <0 01 or P <0 05). In F 2 (2 and 4 mg·kg -1 ) groups serum CK CK MB LDH HBDH GOT concentration and MDA contents were decreased significantly (vs I/R group P <0 01), and SOD increased significantly(vs I/R group P <0 01). The decrease of CK, CK MB, LDH, HBDH, MDA in F 2 (4 mg·kg -1 ) group was more remarkable than that in F 2 (2 mg·kg -1 ) group( P <0 01). CK MB in F 2 (4 mg·kg -1 ) group was lowered than that in Verapamil (2 mg·kg -1 ) group ( P <0 05). For morphology, myocytes of I/R heart showed intracellular edema, disarrangement and rapture of myocardial fiber, damaged mitochondria, marginated and concentrated nucleus. F 2 modified these changes. CONCLUSION F 2 may play an apparent role against rat heart ischemia/reperfusion injury in dose dependent manner.
Keywords:quateranary ammonium salt derivative  myocardial reperfusion injury  creatine kinase isoenzyme MB  superoxide dismutase  malondiadehyde  electron microscopy
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