雷米普利与BQ-123对大鼠在体心肌缺血/再灌注氧化损伤的保护作用

Cardioprotection of ramipril and BQ-123 against myocardial ischemia/reperfusion oxidative injury in vivo in rats

目的研究雷米普利与BQ-123单用及合用对大鼠在体心肌缺血/再灌注损伤的影响,并从氧化-抗氧化角度初步探讨其机制。方法健康♂Wistar大鼠随机分为假手术(Sham)、缺血/再灌注(I/R)、雷米普利(RAM)、BQ-123(BQ)及联合给药(R&B)共5组。除Sham组,其余均行I/R过程。I/R前24h,RAM及R&B组按1mg.kg-1剂量以雷米普利生理盐水溶液灌胃,其余组均以等剂量生理盐水(NS)灌胃;I/R过程中,BQ及R&B组按10μg.kg-1.min-1,于缺血前10min至缺血30min末用注射泵恒速左侧股静脉输入BQ-123生理盐水溶液2ml,其余组均以等剂量NS持续静脉输入。观察动物心率、血压、心电图ST-段变化,记录缺血期室性心律失常(VA);TTC染色检测心肌梗死情况;比色法检测心肌组织中总-超氧化物歧化酶(T-SOD)、锰-超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)活力及丙二醛(MDA)含量。结果与I/R组比较,各给药组ST-段抬高幅度均明显降低、缺血期VA出现时间明显推迟且持续时间明显缩短、心律失常发生率均明显下降、梗死面积明显缩小、心肌组织T-SOD、Mn-SOD及CAT活力均明显升高、MDA含量明显下降。与单用药组比较,联合给药组在VA出现及持续时间、梗死面积、T-SOD和Mn-SOD活力及MDA含量方面变化更为明显。结论雷米普利、BQ-123单用及联合应用均对大鼠在体心肌缺血/再灌注损伤有保护作用,且两药合用在推迟缺血期VA的出现时间,缩短其持续时间,缩小心肌梗死面积,提高心肌组织SOD活力,降低MDA含量方面优于两药各自单用。

Aim To investigate the protection of ramipril,BQ-123 and their combination against myocardial ischemia/reperfusion（I/R）injury in vivo in anesthetized rats,and to explore the mechanism of action of drugs on myocardial oxidation-antioxidation system.Methods Healthy male Wistar rats were divided into 5 groups randomly,sham operated（Sham）group,I/R group,ramipril（RAM）group,BQ-123（BQ）group and ramipril and BQ-123（R＆B）group.All groups but not sham were subjected to I/R procedure.Twenty four hours before ligation,ramipril（1 mg·kg^-1）was intragastrically administered to rats in RAM and R＆B groups.The equal volume of normal saline was given to rats in other groups.BQ-123（10 μg·kg^-1· min^-1）was infused intravenously from 10 min before ligation to the end of 30 min ischemia to rats in BQ and R＆B groups.The equal volume of normal saline was given to other groups.HR,MAP and the change of ST-segment were observed;ventricular arrhythmias were monitored during ischemia;the infarct size was examined by TTC staining;the activity of myocardial T-SOD,Mn-SOD,CAT and the content of MDA were detected by spectrophotometer.Results Compared with I/R group,the elevation of ST-segment was decreased,onset of VPC and VT was delayed,duration of VPC and VT was shortened,incidence of VPC,VT and VF was decreased,IS and IS/AAR were improved,activity of T-SOD,Mn-SOD and CAT was increased,the content of MDA was decreased in RAM,BQ and R＆B groups.Compared with RAM and BQ alone group,onset of VPC and VT,duration of VPC and VT,size,activity of T-SOD and Mn-SOD and content of MDA were changed dramatically in R＆B group.Conclusions Ramipril,BQ-123 and the combined use of these two agents protected myocardium from I/R injury in vivo.The protective effects of the combination on delaying onset of VA,shortening duration of VA,decreasing infarct size and content of MDA,and increasing activity of SOD are better than those of using ramipril or BQ-123 alone.