目标温度控制联合PGE_1对心肺复苏后大鼠脑微血管内皮缺血再灌注损伤的保护

The Protective Effect of Target Temperature Management Combined with Prostaglandin E_1 on Ischemia/Reperfusion Injury of Cerebral Micro-vascular Endothelium of ROSC Rat

目的探讨目标温度控制(TTM)、前列腺素E1(PGE1)及两者联合干预措施对心跳骤停后自主循环恢复(ROSC)大鼠的脑微血管内皮缺血再灌注损伤是否存在保护作用。方法经食道交流电致颤建立ROSC大鼠模型。设立假手术组、ROSC组、PGE1组、TTM组和PGE1/TTM联合干预组。采用HE染色检测脑组织细胞肿胀及微血栓形成情况。脑组织进行CD34/TUNEL荧光双染和血管内皮钙黏蛋白素(VE-cadherin)/血管内皮生长因子受体荧光双染,比较脑微血管内皮细胞损伤程度。运用荧光定量PCR技术测定脑组织匀浆中VE-cadherin和血管细胞黏附分子-1(VCAM-1)的mRNA表达水平。结果 TTM、PGE1及其联合干预措施可以不同程度地减轻脑组织水肿,减少微血栓的形成以及微血管内皮细胞的凋亡,缓解脑微血管内皮细胞VE-cadherin蛋白的破坏,且以联合干预组更为显著。3种干预措施可有效抑制脑组织中VE-cadherin mRNA(0.5h)和VCAM-1mRNA(4h和8h)表达水平的上升(P<0.05)。结论 TTM和PGE1均对ROSC大鼠的脑微血管内皮缺血再灌注损伤具有不同程度保护能力,且两者的联合干预效果较单独干预强。

Objective To investigate the protective effect of target temperature management（TTM）combined with prostaglandin E1（PGE1）on ischemia/reperfusion（I/R）injury of cerebral micro-vascular endothelium cell（CMEC）in the return of spontaneous circulation（ROSC）rats with successful cardiopulmonary resuscitation.Methods Transoesophageal cardiac pacing with alternating current was used to induce ventricular fibrillation in rats.Five groups were set：Sham group（S group）,ROSC group（R group）,PGE1group（P group）,TTM group（T group）and PGE1/TTM group（PT group）.Cell edema and micro-thrombus formation in cerebral tissue were evaluated through HE staining.I/R injury of CMEC was evaluated through CD34/TUNEL and vascular endothelial（VE）-cadherin/VE growth factor receptor double fluorescent immunohistochemistry staining.VE-cadherin mRNA and vascular cell adhesion molecule-1（VCAM-1）mRNA expression in cerebral tissue lysate was analyzed by fluorescence quantitative PCR.Results TTM,PGE1 and PGE1/TTM could significantly improve cerebral interstitial edema,micro-thrombus,and inflammatory cells infiltration in the brain tissue,and reduce the apoptosis and VE-cadherin protein loss of CMEC.PGE1/TTM showed better protective effect.These 3interventions also inhibited the rapid elevation of VE-cadherin mRNA（0.5h）and VCAM-1mRNA（4hand 8h）expression（P〈0.05）,which might indicate the less I/R injury of CMEC of ROSC rat.Conclusion Both PGE1 and TTM could alleviate I/R injury of CMEC from ROSC rat after CPR separately,while PGE1/TTM combined intervention might have synergistic better effect.