氟哌啶醇季铵盐衍生物(F_2)对大鼠心肌缺血再灌注损伤保护作用的研究(英文)

Protective Effect of Quaternary Ammonium Salt Derivative(F_2)ofHaloperidol on Ischemia and Reperfusion Injury in Rat Heart

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保护作用的影响。方法 :大鼠冠状动脉左前降支结扎 3 0min后恢复血液灌注 3 0min ,于缺血前舌下静脉注射不同剂量F2 ( 1mg kg ,2mg kg ,4mg kg)。测定血清CK ,CK·MB、LDH、HBDH、GOH、SOD、MDA的含量 ;观察心肌病理形态学改变。结果 :F2 能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 ,降低脂质过氧化物MDA的产生 ,并呈量效关系 ;透视电子显微镜下可观察到F2 能较好减轻缺血再灌注心肌的形态学改变。结论 :F2

Objective:To study the effect of quaternary ammonium salt derivative(F 2)of haloperidol on rat heart ischemia/reperfusion(I/R)injury.Methods:Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 minutes and restoring blood perfusion for 30 minutes.Three dosages (1mg/kg,2mg/kg,4mg/kg,respectively)of F 2 were 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),malondiadehyde(MDA) concentrations and superoxide dismutase(SOD)activity were measured.The pathologic changes of I/R myocardium were observed on the transmission electron microscopy.Results:F 2 reduced the release of CK,CK MB,LDH,HBDH and GOT from I/R rat hearts,increased the activity of SOD and decreased the MDA product.In F 2 (1mg/kg)group,the serum CK MB,LDH and HBDH concentrations were lowered significantly(vs I/R group P <0 01 or P <0 05).In F 2(2mg/kg and 4mg/kg)groups,serum CK,CK MB,LDH,HBDH and GOT concentrations and MDA content were decreased significantly (vs I/R group P <0 01),and SOD activity increased significantly(vs I/R group P <0 01).The decrease of CK,CK MB,LDH,HBDH and MDA in F 2 (4mg/kg) group was more remarkable than that in F 2(2mg/kg) group( P <0 01).CK MB in F 2 (4mg/kg) group was lower than that in Verapamil(2mg/kg) 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 mollified these changes.Conclusion:F 2 may exert an apparent role against rat heart ischemia/reperfusion injury in dose dependent manner.