ERK抑制剂对心肺复苏后大鼠心肌缺血再灌注损伤和能量代谢的作用研究

目的 探讨 ERK抑制剂 PD98059对于心脏骤停/心肺复苏（CA/CPR）后大鼠心肌能量代谢和心肌缺血再灌注损伤的作用。方法 36只大鼠按随机数字表法分为假手术（Sham）组（n=6）、模型（CA）组（n=15）和 PD98059（PD）组（n=15）。Sham组只单纯行手术操作；CA组和 PD组经食道交流电刺激诱导心室颤动（VF）建立大鼠 CA/CPR模型，恢复自主循环（ROSC）后，PD组立即静脉注射 PD98059（0.3 mg/kg），CA组立即静脉注射等量生理盐水。观察复苏后24 h存活情况，采集血清检测心肌肌钙蛋白 I，同时取心肌组织进行 HE染色、ATP含量测定，并采用蛋白免疫印迹法检测磷酸化 ERK（p-ERK）的表达水平。结果 复苏后 24 h，各组存活情况为 Sham组 6只、CA组 6只、PD组 13只。与Sham组比较，CA和 PD组血清心肌肌钙蛋白 I水平升高；PD组血清心肌肌钙蛋白 I水平较 CA组下降（P＜0.05）。PD组 ATP含量较 CA组明显升高（P＜0.05），心肌病理损伤程度也较 CA组明显减轻。与 Sham组比较，CA和 PD组大鼠心肌组织 p-ERK的表达水平升高；PD组 p-ERK表达水平较 CA组下降（P＜0.05）。结论 ERK抑制剂 PD98059治疗能够改善心肺复苏后心肌能量代谢障碍，减轻心肌缺血再灌注损伤。

Effects of ERK inhibitor on myocardial ischemia reperfusion injury and energy metabolismdysfunction in rats after cardiopulmonary resuscitation

Objective To investigate the effects of ERK inhibitor PD98059 on cardiac energy metabolism andmyocardial ischemia reperfusion injury in rats after cardiac arrest / cardiopulmonary resuscitation (CA / CPR). MethodsThirty-six rats were randomly divided into three groups: Sham group (n=6), PD98059 (PD) group (n=15) and model (CA)group (n=15). Rat model of CA/CPR in PD and CA groups was established by induction of ventricular fibrillation (VF) byelectrical stimulation of the esophagus. Sham group was given operation only. After the restoration of spontaneous circulation(ROSC), PD group was given intravenous injection of PD98059 (0.3 mg / kg) immediately, CA group was given the sameamount of normal saline. Survival was observed for 24 h. Serum samples were collected 24 h after resuscitation to detecttroponin I. Meanwhile, myocardial tissue samples were collected for hematoxylin-eosin (HE) staining and ATP contentdetermination. Western blot assay was used to detect the level of ERK and phosphorylation of ERK (p-ERK). ResultsAfter 24 h, the survival was 6 for Sham group, 6 for CA group and 13 for PD group. The serum level of troponin I wasincreased in CA and PD groups than that of Sham group, and which was decreased in PD group than that of CA group (P＜0.05). The cardiac tissue ATP content was significantly higher in PD group than that of CA group (P＜0.05), and the degreeof myocardial pathological injury was significantly less in PD group than that of CA group. Compared with Sham group, theexpression of myocardial p-ERK was significantly increased in CA and PD groups. The expression of myocardial p-ERK wassignificantly decreased in PD group than that of CA group (P＜0.05). Conclusion The treatment with ERK inhibitorPD98059 can improve the myocardial energy metabolism dysfunction and alleviate the myocardial ischemia reperfusioninjury after cardiopulmonary resuscitation.