CAJ | 학술논문

目的：探讨MAPK信号通路在瑞芬太尼预处理减轻心力衰竭大鼠离体心脏缺血/再灌注损伤中的作用。方法成年♂ SD大鼠,尾静脉注射阿霉素,制备慢性心力衰竭模型,通过随机数字表将54只模型大鼠分为9组( n=6)：假手术组( sham)、缺血/再灌注组( IR)、瑞芬太尼预处理组( RPC)、ERK抑制剂PD98059+RPC组( RPD)、p38抑制剂SB203580+RPC组( RSB)、JNK抑制剂SP600125+RPC组( RSP)以及抑制剂对照组( PD、SB和 SP )。化学比色法检测再灌注5 min和10 min时冠脉流出液中乳酸脱氢酶( LDH)的活性,再灌注末行TTC染色并计算心肌梗死面积,通过Power Lab系统记录血流动力学。结果与IR组相比,RPC可以明显降低梗死面积与缺血危险区的比值( IS/AAR),同时,也可以降低再灌注5 min 及10 min LDH 活性；而 JNK 抑制剂SP600125几乎完全取消 RPC 的保护作用,明显增加 IS/AAR,并升高再灌注5 min LDH活性； ERK抑制剂PD98059也可部分阻断RPC的保护作用；而p38抑制剂SB203580对RPC的保护作用则无明显影响。血流动力学结果显示,与IR相比,RPC及加入MAPK抑制剂后对离体心脏缺血/再灌注损伤后心功能影响差异无统计学意义。结论 JNK 和ERK信号通路可能在瑞芬太尼预处理减轻心力衰竭大鼠离体心脏缺血/再灌注损伤中发挥重要作用。
목적：탐토MAPK신호통로재서분태니예처리감경심력쇠갈대서리체심장결혈/재관주손상중적작용。방법성년♂ SD대서,미정맥주사아매소,제비만성심력쇠갈모형,통과수궤수자표장54지모형대서분위9조( n=6)：가수술조( sham)、결혈/재관주조( IR)、서분태니예처리조( RPC)、ERK억제제PD98059+RPC조( RPD)、p38억제제SB203580+RPC조( RSB)、JNK억제제SP600125+RPC조( RSP)이급억제제대조조( PD、SB화 SP )。화학비색법검측재관주5 min화10 min시관맥류출액중유산탈경매( LDH)적활성,재관주말행TTC염색병계산심기경사면적,통과Power Lab계통기록혈류동역학。결과여IR조상비,RPC가이명현강저경사면적여결혈위험구적비치( IS/AAR),동시,야가이강저재관주5 min 급10 min LDH 활성；이 JNK 억제제SP600125궤호완전취소 RPC 적보호작용,명현증가 IS/AAR,병승고재관주5 min LDH활성； ERK억제제PD98059야가부분조단RPC적보호작용；이p38억제제SB203580대RPC적보호작용칙무명현영향。혈류동역학결과현시,여IR상비,RPC급가입MAPK억제제후대리체심장결혈/재관주손상후심공능영향차이무통계학의의。결론 JNK 화ERK신호통로가능재서분태니예처리감경심력쇠갈대서리체심장결혈/재관주손상중발휘중요작용。
Aim To investigate the roles of mitogen-ac-tivated protein kinases ( MAPK ) pathways in the pro-tective effects of remifentanil preconditioning against is-chemia/reperfusion injury of isolated heart in rats with heart failure. Methods Adult male SD rats were injected with adriamycin via tail vein for 6 weeks to induce heart failure. The rats were confirmed chronic heart failure through echocardiography and randomly divided into 9 groups(n=6)as follows: sham group, ischemia/reperfusion group ( IR) , remifentanil precon-ditioning group( RPC) , ERK inhibitor PD98059+RPC group ( RPD ) , p38 inhibitor SB203580 +RPC group ( RSB ) , JNK inhibitor SP600125 + RPC group ( RSP ) , and the inhibitor control groups ( PD , SB and SP) . All hearts were linked to the Langendorff ap-paratus. The coronary effluent was collected to detect the activity of lactate dehydrogenase ( LDH ) at base-line, 5 min and 10 min after reperfusion, respectively. Infarct size ( IS) and area at risk ( AAR) were deter-mined by 2, 3, 5-triphenyl-tetrazolium (TTC) staining at the end of reperfusion. Left ventricular developed pressure ( LVDP), ± dp/dtmax and heart rate ( HR) were recorded to evaluate cardiac function in each group. Results When compared with IR group, RPC significantly reduced IS / AAR and decreased the ac-tivity of LDH at 5 min and 10 min after reperfusion. However, SP600125 almost thoroughly abolished the protective effects of RPC, as evidenced by the in-creased value of IS / AAR and the high activity of LDH. In addition, PD98059 also partly blocked the effects of RPC, while SB203580 showed no influence on RPC. Meanwhile, the hemodynamic parameters such as LVDP, HR and ± dp/dtmax were not signifi-cantly different in any group except sham group. Con-clusion JNK and ERK pathways may play an impor-tant role in cardioprotective effects of remifentanil pre-conditioning against ischemia/reperfusion injury in rats with heart failure.