MAPK通路在瑞芬太尼预处理减轻心衰大鼠离体心脏缺血/再灌注损伤中的作用

Role of MPAK pathways in the protective effects of remifentanil preconditioning against ischemia /reperfusion injury of isolated heart in rats with heart failure

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5min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。

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＆amp;nbsp;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）, ＆#177; 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 ＆#177; 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.