兔心肺转流模型中乙醛脱氢酶2活化的心肌保护研究

Myocardial protection through aldehyde dehydrogenase 2 activation during rabbit cardiopulmonary bypass

目的有毒醛的堆积可产生心血管毒性,乙醛脱氢酶2(ALDH2)可有效清除醛类物质,本研究旨在兔心肺转流(CPB)模型中探索ALDH2活化的心肌保护作用。方法21只新西兰白兔随机分为三组:CPB不停跳组(C组)、停跳组(CA组)、停跳+Alda-1组(CAA组),Alda-1为ALDH2特异性激动剂,另随机选取21只作为供血兔。右腋动脉插管及右房插管建立CPB模型,主动脉阻断120 min后开放,生命体征平稳后停机,恢复心肌灌注120 min测定心功能并取左室心肌组织,测定ALDH2的含量及活性、4-羟基壬烯醛(4-HNE)含量、丙二醛(MDA)含量、氧化型与还原型谷胱甘肽比值(GSH/GSSG)、蛋白羰基含量,检测不同时点血气及血清肌酸磷酸激酶同工酶(CKMB)值。结果各组间ALDH2含量无明显差异,CAA组与CA组相比ALDH2活性明显增加(P<0.001),4-HNE、MDA含量在CA组较C组增加(4-HNE:P<0.001,MDA:P=0.001),CAA组较CA组明显下降(4-HNE:P=0.013,MDA:P<0.001)。CAA组较CA组心肌蛋白羰基水平、血清CKMB明显降低,GSH/GSSH生成增加(P<0.05),CAA组左室压力形成最大速率较CA组明显升高(P=0.040),但三组间左室舒张末压、左室收缩末压、左室压力形成最小速率无统计学差异。结论CPB期间ALDH2活化可加强有毒醛清除,增强心肌抗氧化损伤能力,减轻心肌的氧化应激,改善心肌收缩功能。

Objective Toxic aldehyde is related to myocardial injury,which could be eliminated by mitochondrial aldehyde dehydrogenase 2(ALDH2).Our study was proposed to demonstrate myocardial protective effect by ALDH2 activation during cardiopulmonary bypass(CPB).Methods Twenty-one New Zealand white rabbits were randomly divided into cardiopulmonary bypass group(C group),cardioplegic arrest group(CA group),cardioplegic arrest and Alda-1 group(CAA group).Another 21 rabbits were sacrificed as blood donors.Alda-1 is a special activator of ALDH2.Animals in group C were treated with normothermic CPB without cardiac arrest,animals in groups CA and CAA were treated with CPB,during which the heart underwent 120 min of global ischemia and 120 min of reperfusion.Both ALDH2 level and activity were determined,as well as aldehydes(4-HNE and MDA),glutathione/oxidized glutathione ratios(GSH/GSSG),protein carbonyl,creatine kinase MB(CKMB),and cardiac function.Results Administration of Alda-1 increased ALDH2 activity,increased GSH/GSSG,but decreased 4-hydroxynonenal and malondialdehyde(all P<0.05).Increased ALDH2 activity attenuated the elevation of CKMB and protein carbonyl.Dp/dtmaxwas increased in CAA group compared with CA group(P=0.040).There was no significant difference in LVEDP,LVESP,and dp/dtminamong three groups.Conclusion ALDH2 activation protects heart from I/R injury during CPB by elimination of toxic aldehydes and alleviation of oxidative stress,subsequently improve its contractive function.