中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2010年
1期
91-94
,共4页
雷诺嗪%后处理%心肌%再灌注损伤%凋亡%心肌再灌注损伤营救激酶%线粒体通透性转换孔道
雷諾嗪%後處理%心肌%再灌註損傷%凋亡%心肌再灌註損傷營救激酶%線粒體通透性轉換孔道
뢰낙진%후처리%심기%재관주손상%조망%심기재관주손상영구격매%선립체통투성전환공도
ranolazine%postconditioning%myocardial%reperfusion injury%apoptosis%RISK%MPTP
目的 探讨雷诺嗪后处理对大鼠离体心脏缺血/再灌注时心肌细胞凋亡与再灌注损伤营救激酶(reperfusion injurysalvage kinase,RISK)及其线粒体渗透性转换孔道(mitochondrial permeability transition pore,MPTP)的影响.方法 建立Langendorff离体心脏灌流模型.56只SD大鼠随机分为8组(n=7):缺血/再灌注组(I/R组)、雷诺嗪后处理组(RPostC组)、雷诺嗪+atractyloside组(RA组)、雷诺嗪+PD98059组(RP组)、雷诺嗪+wortmannin(RW组)、atractyloside组(A组)、P组和W组.各组均缺血30 min/再灌注15 min,药物后处理时间为再灌注开始后10 min.用TUNEL法检测再灌注末心肌凋亡并计算凋亡指数(apoptotic index,AI),分光光度计测MPTP开放程度,Western blot法测p-AKT和p-ERK1/2的表达水平.结果 与IR组比较,RPostC组心肌细胞AI和MPTP开放程度下降(P<0.05),RPostC、RA、RP和RW组p-AKT、p-ERK1/2蛋白表达升高(P<0.05),其它组间差异无统计学意义(P>0.05);与RPostC组比较,RA、RP、RW、A、P和W组AI和MPTP开放程度升高(P<0.05),RP、RW、A、P和W组p-AKT、p-ERK1/2蛋白表达下降(P<0.05),RA组p-AKT、p-ERK1/2蛋白表达差异无统计学意义(P>0.05);与RA组比较,RP、RW、A、P和W组AI和MPTP开放程度差异无统计学意义,p-AKT、p-ERK1/2蛋白表达下降(P<0.05).结论 雷诺嗪后处理对大鼠离体缺血/再灌注心肌具有明显的抗凋亡作用,其机制可能与其激活RISK途径和抑制MPTP开放有关.
目的 探討雷諾嗪後處理對大鼠離體心髒缺血/再灌註時心肌細胞凋亡與再灌註損傷營救激酶(reperfusion injurysalvage kinase,RISK)及其線粒體滲透性轉換孔道(mitochondrial permeability transition pore,MPTP)的影響.方法 建立Langendorff離體心髒灌流模型.56隻SD大鼠隨機分為8組(n=7):缺血/再灌註組(I/R組)、雷諾嗪後處理組(RPostC組)、雷諾嗪+atractyloside組(RA組)、雷諾嗪+PD98059組(RP組)、雷諾嗪+wortmannin(RW組)、atractyloside組(A組)、P組和W組.各組均缺血30 min/再灌註15 min,藥物後處理時間為再灌註開始後10 min.用TUNEL法檢測再灌註末心肌凋亡併計算凋亡指數(apoptotic index,AI),分光光度計測MPTP開放程度,Western blot法測p-AKT和p-ERK1/2的錶達水平.結果 與IR組比較,RPostC組心肌細胞AI和MPTP開放程度下降(P<0.05),RPostC、RA、RP和RW組p-AKT、p-ERK1/2蛋白錶達升高(P<0.05),其它組間差異無統計學意義(P>0.05);與RPostC組比較,RA、RP、RW、A、P和W組AI和MPTP開放程度升高(P<0.05),RP、RW、A、P和W組p-AKT、p-ERK1/2蛋白錶達下降(P<0.05),RA組p-AKT、p-ERK1/2蛋白錶達差異無統計學意義(P>0.05);與RA組比較,RP、RW、A、P和W組AI和MPTP開放程度差異無統計學意義,p-AKT、p-ERK1/2蛋白錶達下降(P<0.05).結論 雷諾嗪後處理對大鼠離體缺血/再灌註心肌具有明顯的抗凋亡作用,其機製可能與其激活RISK途徑和抑製MPTP開放有關.
목적 탐토뢰낙진후처리대대서리체심장결혈/재관주시심기세포조망여재관주손상영구격매(reperfusion injurysalvage kinase,RISK)급기선립체삼투성전환공도(mitochondrial permeability transition pore,MPTP)적영향.방법 건립Langendorff리체심장관류모형.56지SD대서수궤분위8조(n=7):결혈/재관주조(I/R조)、뢰낙진후처리조(RPostC조)、뢰낙진+atractyloside조(RA조)、뢰낙진+PD98059조(RP조)、뢰낙진+wortmannin(RW조)、atractyloside조(A조)、P조화W조.각조균결혈30 min/재관주15 min,약물후처리시간위재관주개시후10 min.용TUNEL법검측재관주말심기조망병계산조망지수(apoptotic index,AI),분광광도계측MPTP개방정도,Western blot법측p-AKT화p-ERK1/2적표체수평.결과 여IR조비교,RPostC조심기세포AI화MPTP개방정도하강(P<0.05),RPostC、RA、RP화RW조p-AKT、p-ERK1/2단백표체승고(P<0.05),기타조간차이무통계학의의(P>0.05);여RPostC조비교,RA、RP、RW、A、P화W조AI화MPTP개방정도승고(P<0.05),RP、RW、A、P화W조p-AKT、p-ERK1/2단백표체하강(P<0.05),RA조p-AKT、p-ERK1/2단백표체차이무통계학의의(P>0.05);여RA조비교,RP、RW、A、P화W조AI화MPTP개방정도차이무통계학의의,p-AKT、p-ERK1/2단백표체하강(P<0.05).결론 뢰낙진후처리대대서리체결혈/재관주심기구유명현적항조망작용,기궤제가능여기격활RISK도경화억제MPTP개방유관.
Aim To investigate the effect of ranolazine postconditioning on myocardial apoptosis, the reperfusion injurysalvage kinase and the opening of MPTP in isolated rat hearts subjected to ischemia and reperfusion.Methods The langendorff mode was set up.Fifty-five SD rat hearts were randomly divided into 8 groups (n=7): ischema and reperfusion (I/R group),20 μmol·L~(-1) ranolazine postconditioning group(RPostC),ranolazine and the specific MPTP opener atractyloside group (RA), ranolazine and the specific ERK1/2 inhibitor PD98059 group (RP), ranolazine and the specific PI3K inhibitor PD98059 wortmannin group(RW), atractyloside group(A), PD98059 group (P) and wortmannin group (W). The isolated hearts were subjected to 30 minutes ischemia,10minutes drug postconditioning and 5 mitutes K-H buffer reperfusion.Myocardial apoptosis (TUNEL-positive cells), apoptotic index (AI), the opening of MPTP (spectrophotometry) and the The expression of p-AKT and p-ERK1/2 protein were measured at the end of reperfusion in each group.Results Compared with IR group, Myocardial AI and opening of MPTP were decreased in RPostC groups (P<0.05), the expression of p-AKT, p-ERK1/2 protein were increased in RPostC, RA, RP, and RW groups (P<0.05).There were no significant differences in other groups(P>0.05). Compared with RPostC group, Myocardial AI and opening of MPTP were increased in RA, RP, RW, A, P and W groups (P<0.05), and the expression of p-AKT、p-ERK1/2 protein were decreased in RP, RW, A, P and W groups (P<0.05). There were no significant differences of the expressions of p-AKT,p-ERK1/2 protein in RA groups (P>0.05). Compared with RA group, there were no significant differences in myocardial AI and opening of MPTP (P>0.05) and the expression of p-AKT and p-ERK1/2 protein were decreased in RP, RW, A, P and W groups (P<0.05).Conclusions Ranolazine postconditioning can attenuate myocardial apoptosis in isolated rat hearts subjected to ischemia and reperfusion via activation RISK pathway and inhibition of the opening of MPTP.
