Zhou Tao, Guo Shanliang, Wang Shaolin, Li Qiong, Zhang Mingsheng
Department of Anesthesiology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4307-4311. doi: 10.3892/etm.2017.5078. Epub 2017 Aug 30.
This study was designed to investigate possible protective effects of sevoflurane on myocardial ischemia-reperfusion injury (MIRI) and its impact on expression of HIF-1α and caspase-3 in rats, so as to provide new insights for the treatment of MIRI. Forty SD rats were randomly divided into four groups (n=10) including Sham operation (Sham), ischemia-reperfusion (IR), sevoflurane preconditioning group (Sevo-Pre) and sevoflurane post-conditioning (Sevo-Post) groups. Perfusion was performed using heart perfusion. The baseline values of cardiac function were recorded in each group at the end of balanced perfusion and after 60 min of reperfusion. Myocardial infarct size (MIS) was calculated at the end of perfusion using TTC staining. Levels of HIF-1α and caspase-3 protein and HIF-1α (western blotting) and Bcl-2 mRNA (RT-qPCR) were detected at the end of reperfusion. Our results showed no significant differences in cardiac function between the groups at the end of the balanced perfusion. After reperfusion for 60 min, however, the cardiac functions of the Sevo-Pre and Sevo-Post groups were significantly better than those in the IR group, and the MIS at the end of reperfusion was significantly decreased. Western blotting and RT-qPCR showed that expression of HIF-1α protein was significantly increased, expression of caspase-3 protein was significantly decreased and expression of HIF-1α and Bcl-2 mRNA were significantly increased in Sevo-Pre and Sevo-Post groups compared with the levels in the IR group at the end of reperfusion. There were no significant differences in experimental results between Sevo-Pre and Sevo-Post groups. Our data support the idea that sevoflurane can improve MIRI in rats by improving cardiac function and reducing MIS. This protective effect seems to be achieved by activation of HIF-1α and inhibition of caspase-3.
本研究旨在探讨七氟醚对大鼠心肌缺血再灌注损伤(MIRI)的可能保护作用及其对大鼠缺氧诱导因子-1α(HIF-1α)和半胱天冬酶-3(caspase-3)表达的影响,为MIRI的治疗提供新的思路。40只SD大鼠随机分为四组(n = 10),包括假手术组(Sham)、缺血再灌注组(IR)、七氟醚预处理组(Sevo-Pre)和七氟醚后处理组(Sevo-Post)。采用心脏灌注法进行灌注。在平衡灌注结束时和再灌注60分钟后记录每组的心功能基线值。灌注结束时用TTC染色计算心肌梗死面积(MIS)。再灌注结束时检测HIF-1α和caspase-3蛋白水平以及HIF-1α(蛋白质印迹法)和Bcl-2 mRNA(逆转录定量聚合酶链反应)。结果显示,平衡灌注结束时各组心功能无显著差异。然而,再灌注60分钟后,Sevo-Pre组和Sevo-Post组的心功能明显优于IR组,再灌注结束时的MIS显著降低。蛋白质印迹法和逆转录定量聚合酶链反应显示,与再灌注结束时IR组水平相比,Sevo-Pre组和Sevo-Post组HIF-1α蛋白表达显著增加,caspase-3蛋白表达显著降低,HIF-1α和Bcl-2 mRNA表达显著增加。Sevo-Pre组和Sevo-Post组实验结果无显著差异。我们的数据支持七氟醚可通过改善心功能和降低MIS来改善大鼠MIRI的观点。这种保护作用似乎是通过激活HIF-1α和抑制caspase-3来实现的。