Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model.
Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model.
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DOI：
10.1155/2016/6190504
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发表时间：
2016
影响因子：
--
通讯作者：
Wang HJ
中科院分区：
文献类型：
--
作者：
Kang PF;Wu WJ;Tang Y;Xuan L;Guan SD;Tang B;Zhang H;Gao Q;Wang HJ
观察糖尿病(DM)大鼠心脏缺血/再灌注(I/R)干预后线粒体乙醛脱氢酶2(ALDH2)的变化，并分析其机制。DM大鼠体外心脏局部缺血30 ，再灌流120 ，用ALDH2激活剂乙醇(EtoH)预处理，高糖(HG)条件下心肌细胞用ALDH2激活剂Alda-1预处理。对照组I/R组心肌组织结构出现塌陷。与对照组I/R组比较，DM I/R组大鼠左心各指标、超氧化物歧化酶活性、Bcl2/Bax基因表达水平、ALDH2基因表达水平及蛋白表达均降低，LDH和MDA含量升高，心肌结构损伤加重。经乙醇预处理后，DM I/R大鼠左室心功能参数、心肌组织结构损伤减轻，心肌组织超氧化物歧化酶、Bcl2/Bax、ALDH2表达增加，LDH、MDA减少。与DM+Etoh I/R组相比，ALDH2非特异性阻断剂氰胺、PTP开放剂苍术苷和PI3K抑制剂Wortmannin组均能降低心肌损伤程度，降低心肌组织中的SOD、Bcl2/Bax和ALDH2，增加LDH、MDA和心肌损伤。心肌细胞在HG状态下，CCK-8活性和ALDH2蛋白表达降低。ALDA-1使CCK-8和ALDH2升高。提示糖尿病I/R大鼠ALDH2表达增强可能通过激活PI3K和抑制mitoPTP开放发挥心脏保护作用。
The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.
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影响因子：
10.8
作者：
Lim, Shiang Y.;Davidson, Sean M.;Hausenloy, Derek J.;Yellon, Derek M.
通讯作者：
Yellon, Derek M.
影响因子：
9.3
作者：
Budas, Grant R.;Disatnik, Marie-Helene;Mochly-Rosen, Dana
通讯作者：
Mochly-Rosen, Dana
影响因子：
24
作者：
Ma, Heng;Li, Ji;Ren, Jun
通讯作者：
Ren, Jun
影响因子：
5
作者：
Churchill, Eric N.;Disatnik, Marie-Helene;Mochly-Rosen, Daria
通讯作者：
Mochly-Rosen, Daria
影响因子：
5
作者：
Budas GR;Disatnik MH;Chen CH;Mochly-Rosen D
通讯作者：
Mochly-Rosen D