新化合物TG-6对大鼠心肌缺血-再灌注损伤的保护作用  

Protective effects of 3-nitro-4-{[4-(2,3,4-trimethoxybenzyl)piperazin-1-yl] methyl}-benzoylguanidine tartrate(TG-6) on myocardial ischemia-reperfusion injury in rats

作　　者：王寅[1] 龚国清[1] 徐云根[2] 杨文辉[1] 周怡[1] WANG Yin;GONG Guoqing;XU Yungen(Department of Pharmacology,China Pharmaceutical University,Nanjing 210009,CHINA)

机构地区：[1]中国药科大学药理学教研室,南京市210009 [2]中国药科大学药物化学教研室

出　　处：《江苏医药》2011年第12期1371-1374,共4页Jiangsu Medical Journal

基　　金：国家自然科学基金资助项目(30672512)

摘　　要：目的探讨新化合物3-硝基-4-{[4-(2,3,4-三甲氧基苯基)哌嗪-1-基]甲基}-苯甲酰基胍(TG-6)对大鼠心肌缺血-再灌注(I-R)损伤的保护作用。方法结扎大鼠冠状动脉左前降支40 min,再灌注120 min建立心肌I-R损伤模型。48只大鼠分为A组(假手术组)、B组(I-R模型组)、C组(模型组+卡立泊来德1 mg/kg)、D组(模型组+TG-61 mg/kg)、E组(模型组+TG-60.5 mg/kg)、F组(模型组+TG-60.25 mg/kg),每组8只。观察TG-6对大鼠心功能学、心肌梗死面积及血清生化指标的影响。结果与B组比较,D、E、F组左心室内压最大上升与下降速率(±dP/dtmax)、血清超氧化物歧化酶(SOD)活力增高,左心室舒张末期压力(LVEDP)、血清肌酸激酶(CK)活力、乳酸脱氢酶(LDH)活力、丙二醛(MDA)含量降低(P<0.05);D、E组心率、左心室内压(LVSP)增加,心肌梗死面积缩小(P<0.05)。结论TG-6明显减轻大鼠心肌I-R损伤,有望成为治疗心肌I-R损伤新型药物。Objective To investigate the protective effects of 3-nitro-4-{[4-(2,3,4-trimethoxybenzyl)piperazin-1-yl]methyl}-benzoylguanidine tartrate(TG-6)on myocardial ischemia-reperfusion(I-R)injury in rats.Methods Ligation of left anteriordescending coronary artery for 40min and reperfusion for 120min were performed in rats to establish myocardial I-R injury model.Forty-eight healthy Wistar rats were randomly divided into 6 groups of A(sham operated),B(I-R model),C(additionally treated by cariporide 1mg/kg),D(additionally treated by TG-61mg/kg),E(additionally treated by TG-60.5mg/kg)and F(additionally treated by TG-60.25mg/kg)with 8 rats each.The influence of TG-6 on cardiac function,myocardial infarction area and serum biochemical indicators were observed.Results Compared with group B,maximum positive and negative dP/dt(±dP/dtmax)and superoxide dismutase(SOD)activity were increased,while left ventricular end-diastolic pressure(LVEDP),creatine kinase(CK)activity,lactate dehydrogenase(LDH)activity and malondialdehyde(MDA)content were decreased in groups of D,E and F(P〈0.05),heart rate and left ventricular systolic pressure(LVSP)were increased,while myocardial infarction area was reduced in groups of D and E(P〈0.05).Conclusion TG-6 is able to alleviate myocardial I-R injury in rats,which is expected to become a novel drug in the treatment of myocardial I-R injury.

关 键 词：3-硝基-4-{[4-(2 3 4-三甲氧基苯基)哌嗪-1-基]甲基}-苯甲酰基胍 心肌缺血-再灌注损伤 

分 类 号：R965[医药卫生—药理学]