CAJ | 학술논문

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24 h,RAM及R&B组按1 mg·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10 μg·kg~(-1)·min-1,于缺血前10 min至缺血30 min末用注射泵恒速左侧股静脉输入BQ-123生理盐水溶液2 ml,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.
목적 연구뢰미보리여BQ-123단용급합용대대서재체심기결혈/재관주손상적영향,병종양화-항양화각도초보탐토기궤제.방법 건강♂Wistar대서수궤분위가수술(Sham)、결혈/재관주(I/R)、뢰미보리(RAM)、BQ-123(BQ)급연합급약(R&B)공5조.제Sham조,기여균행I/R과정.I/R전24 h,RAM급R&B조안1 mg·kg~(-1)제량이뢰미보리생리염수용액관위,기여조균이등제량생리염수(NS)관위;I/R과정중,BQ급R&B조안10 μg·kg~(-1)·min-1,우결혈전10 min지결혈30 min말용주사빙항속좌측고정맥수입BQ-123생리염수용액2 ml,기여조균이등제량NS지속정맥수입.관찰동물심솔、혈압、심전도ST-단변화,기록결혈기실성심률실상(VA);TTC염색검측심기경사정황;비색법검측심기조직중총-초양화물기화매(T-SOD)、맹-초양화물기화매(Mn-SOD)、과양화경매(CAT)활력급병이철(MDA)함량.결과 여I/R조비교,각급약조ST-단태고폭도균명현강저、결혈기VA출현시간명현추지차지속시간명현축단、심률실상발생솔균명현하강、경사면적명현축소、심기조직T-SOD、Mn-SOD급CAT활력균명현승고、MDA함량명현하강.여단용약조비교,연합급약조재VA출현급지속시간、경사면적、T-SOD화Mn-SOD활력급MDA함량방면변화경위명현.결론 뢰미보리、BQ-123단용급연합응용균대대서재체심기결혈/재관주손상유보호작용,차량약합용재추지결혈기VA적출현시간,축단기지속시간,축소심기경사면적,제고심기조직SOD활력,강저MDA함량방면우우량약각자단용.
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.