CAJ | 학술논문

目的评价七氟醚后处理对大鼠缺血再灌注心肌细胞胀亡和凋亡的影响及细胞外信号调节激酶(ERK) 1/2信号转导通路在其中的作用.方法取Langendorff离体灌注模型成功的大鼠心脏72个,采用随机数字表法分为6组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、七氟醚后处理组(SP组)、ERK1/2抑制剂PD98059组(PD组)、PD98059溶剂二甲基亚砜组(DMSO组)和七氟醚后处理+ PD98059组(SP+ PD组).除S组,其余各组心脏缺血30 min,再灌注2h.SP组、DMSO组和PD组分别于缺血末至再灌注15 min灌注经3.0％七氟醚、DMSO(＜ 0.2％)和PD98059(20 μmol/L)饱和的K-H液,随后更换为正常K-H液再灌注105 min.SP+ PD组于缺血末至再灌注15 min灌注经3.0％七氟醚和PD98059(20 μmol/L)饱和的K-H液.再灌注末测定心肌梗死体积,采用Western blot法检测porimin和caspase-8蛋白表达水平.结果与S组比较,其余各组心肌梗死体积增加,porimin和caspase-8表达上调(P＜0.05)；与I/R组比较,SP组梗死体积减少,porimin和caspase-8表达下调(P＜0.05),其余各组各指标差异无统计学意义(P＞0.05).结论七氟醚后处理可激活ERK1/2信号转导通路,抑制心肌细胞胀亡和凋亡,从而减轻大鼠离体心脏缺血再灌注损伤.
목적 평개칠불미후처리대대서결혈재관주심기세포창망화조망적영향급세포외신호조절격매(ERK) 1/2신호전도통로재기중적작용.방법 취Langendorff리체관주모형성공적대서심장72개,채용수궤수자표법분위6조(n=12):가수술조(S조)、결혈재관주조(I/R조)、칠불미후처리조(SP조)、ERK1/2억제제PD98059조(PD조)、PD98059용제이갑기아풍조(DMSO조)화칠불미후처리+ PD98059조(SP+ PD조).제S조,기여각조심장결혈30 min,재관주2h.SP조、DMSO조화PD조분별우결혈말지재관주15 min관주경3.0％칠불미、DMSO(＜ 0.2％)화PD98059(20 μmol/L)포화적K-H액,수후경환위정상K-H액재관주105 min.SP+ PD조우결혈말지재관주15 min관주경3.0％칠불미화PD98059(20 μmol/L)포화적K-H액.재관주말측정심기경사체적,채용Western blot법검측porimin화caspase-8단백표체수평.결과 여S조비교,기여각조심기경사체적증가,porimin화caspase-8표체상조(P＜0.05)；여I/R조비교,SP조경사체적감소,porimin화caspase-8표체하조(P＜0.05),기여각조각지표차이무통계학의의(P＞0.05).결론 칠불미후처리가격활ERK1/2신호전도통로,억제심기세포창망화조망,종이감경대서리체심장결혈재관주손상.
Objective To evaluate the effects of sevoflurane postconditioning on the oncosis and apoptosis in cardiomyocytes during ischemia-reperfusion (I/R) in isolated rat hearts and the role of extracellular signalregulated protein kinase 1/2 (ERK1/2) signal transduction pathway in it.Methods Seventy-two isolated rat hearts perfused in a Langendorff apparatus were randomly divided into 6 groups (n =12 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),sevoflurane postconditioning group (group SP),PD98059 vehicle dimethyl sulfoxide (DMSO) group (group DMSO),selective ERK1/2 inhibitor PD98059 group (group PD),and sevoflurane postconditioning + PD98059 group (group SP + PD).The hearts were subjected to ischemia for 30 min followed by 2 h reperfusion in the other groups except group S.In SP,DMSO and PD groups,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane,DMSO (＜0.2％) and PD98059 (20 μmol/L),respectively,for 15 min starting from the end of ischemia until 15 min of reperfusion,and then with plain K-H solution for 105 min.In group SP+ PD,the hearts were perfused with K-H solution saturated with 3.0％ sevoflurane and PD98059 for 15 min starting from the end of ischemia until 15 min of reperfusion.Myocardial infarct size and expression of porimin and caspase-8 proteins (by Western blot) were measured at the end of reperfusion.Results Compared with S group,the myocardial infarct size was significantly increased,and the expression of porimin and caspase-8 proteins was up-regulated in the other groups (P ＜ 0.05).Compared with I/R group,the myocardial infarct size was significantly decreased,and the expression of porimin and caspase-8 proteins was down-regulated in group SP (P ＜ 0.05),and no significant changes were found in the other groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can activate ERK1/2 signal transduction pathway and inhibit the oncosis and apoptosis in cardiomyocytes,thus attenuating I/R injury in isolated rat hearts.