α7烟碱样乙酰胆碱受体激动剂后处理对大鼠在体心肌缺血/再灌注损伤的影响

α7nAChR agonist postconditioning attenuates rat myocardia ischemia reperfusion injury in vivo

目的 观察α7烟碱样乙酰胆碱受体（α7 nicotinic acetylcholine receptor,α7nAChR）激动剂后处理对大鼠在体心肌缺血/再灌注损伤（ischemia reperfusion injurv,IRI）的影响.方法 将40只SD大鼠采用计算机产生随机数法平均分为假手术组（S组）、缺血/再灌注组（IR组）、缺血预处理组（IPC组）和α7nAChR激动剂后处理组（PNU组）,每组10只.实验中记录缺血期和再灌注初期心律失常,测定冉灌注30 min和180 min时的肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白介素-6（interleukin-6,IL-6）、高迁移率组蛋白1（high mobilitv group box 1 protein,HMGB1）和肌钙蛋白Ⅰ（troponin Ⅰ,TnI）血清浓度,实验结束取心脏,采用伊文思蓝和1%TTC双重染色法测量心肌梗死面积.结果 IR组,IPC组和PNU组的心肌梗死面积值分别为（78.4±16.1）%、（35.3±9.4）%和（60.4±7.0）%,且3组的TnI血清浓度分别为（1.02±0.12）μg/L,（0.25±0.03）μg/L和（0.17±0.04）μg/L与IR组相比,IPC组和PNU组心肌梗死面积（infarct size,IS%）显著减小、TnI血清浓度显著降低,IPC组灌注30min时TNF-α、IL-6血清浓度以及再灌注180 min时TNF-α和HMCB1血清浓度显著降低,PNU组再灌注30 min和180 min时TNF-α、IL-6和再灌注180 min时HMCB1血清浓度显著降低.与IPC组相比,PNU组IS%显著增大,但血清TnI浓度显著降低,冉灌注30 min时TNF-α血清浓度以及再灌注180 min时TNF-α、IL-6和HMCB1血清浓度显著降低,但再灌注30 min时IL-6血清浓度显著升高.结论 在大鼠在体心肌缺血/冉灌注损伤模型,α7nAChR激动剂后处理可通过抑制炎症反应获得心肌保护效应、但其心肌保护效应较缺血预处理弱.

Objective To observe the cardioprotective effects of α7 nicotinic acetylcholine receptor （α7nAChR） agonist postconditioning on myocardial ischemia reperfusion injury （IRI） in rat models in vivo. Methods Forty SD rats were randomly divided into four groups （n=10）： sham group（ S group）, ischemia reperfusion group（ IR group）, ischemia preconditioning group（ IPC group） and α7nAChR agouist postconditioning group （PNU group）. Incidence of arrhythmia was recorded during the period of ischemia and onset of reperfusion. Serum concentrations of tumor necrosis factor-o（TNF-α）, interlerkin-6（IL-6） were assayed at 30 min and 180 min after reperfusion, and serum concentrations of high mobility group box 1 protein（HMGB1 ） and troponin I（TnI） at 180 min after reperfusion were tested in all groups. At the end of experiment, infarction sizes were assessed from excised hearts by Evans blue and 1 % triphenyltetrazolium chloride staining. Results The infarct size（IS%） of IR,IPC and PNU groups were（78.4±16.1 ）%, （35.3±9.4）%and （60.4±7.0）% respectively,and the serum concentration of TnI in these groups were （1.02±0.12） μg/L,（0.25±0.03） μg/L and （0.17±0.04） μg/L. respectively. Compared to IR group, the IS% and serum concentration of TnI in IPC group and PNU group were significantly reduced. The serum concentrations of TNF-α and IL-6 at 30 min of reperfusion and TNF-α and HMGBI at 180 min of reperfusion in IPC group and PNU group were significantly lower than these in IR group. And the serum level of IL-6 at 180 min of reperfusion in PNU group was also significantly decreased compared to IR group. Compared to IPC group, the infarct size of PNU group was significantly increased, however the serum concentration of TnI of PNU group was significantly decreased. Although the serum concentration of IL-6 at 30 min of reperfusion in PNU group was significantly higher than that in IPC group, the serum concentrations of TNF-α at 30 min of re perfusion and TNF-α, IL-6 and HMGB1 at 180 min of reperfusion were significantly decreased. Conclusion In rat in vivo models of myocardial ischemia reperfusion injury, α7nAChR agonist postconditioning could inhibit the reperfusion-induced inflammatory response to realize the cardioprotection. However the effect of infarct size limiting induced by α7nAChR postconditioning is less powerful than that of ischemia preconditioning.