烟碱激活胆碱能抗炎通路对大鼠心肌缺血-再灌注损伤的保护作用

摘要

目的 探讨烟碱对大鼠心肌缺血-再灌注损伤(MIRI)的保护作用及其机制.方法 采用左冠状动脉前降支结扎-开放法建立大鼠心肌MIRI动物模型.30只大鼠随机分为对照组(假手术组)、缺血再灌注组、烟碱400 μg/kg组、烟碱200 μg/kg组和烟碱40 μg/kg组共5组(每组6只).观察心肌缺血区和梗死区面积、心肌组织病理学变化,酶联免疫吸附法(ELISA)检测血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平.结果 与缺血再灌注组比较,烟碱400 μg/kg组心肌细胞梗死面积明显减小,差异有统计学意义(P<0.01).病理学观察显示,烟碱400 μg/kg组心肌组织较缺血再灌注组炎性改变明显减轻.缺血再灌注组大鼠4 h血浆TNF-α水平明显高于对照组(P<0.01);烟碱400 μg/kg组4 h血浆TNF-α水平、200 μg/kg组和40 μg/kg组均明显低于缺血再灌注组(P<0.01).缺血再灌注组大鼠4 h血浆IL-6水平明显高于对照组(P<0.01).烟碱400 μg/kg组和200 μg/kg组4 h血浆IL-6水平均明显低于缺血再灌注组(P<0.01).烟碱400 μg/kg组与40 μg/kg组血浆IL-6水平差异有统计学意义(P<0.05).结论 烟碱作用于心肌缺血再灌注大鼠后,明显减轻心肌细胞损伤,减小缺血面积,对心肌组织具有保护作用.其机制在于激活胆碱能抗炎通路,降低体内炎性细胞因子水平而发挥抗炎作用.%Objective To investigate the protective effect of nicotine on myocardium ischemia - reperfusion injury hy cholinergic anti - inflammatory pathway in rat. Methods 30 rats were randomly divided into 5 groups, each group 6 rats. ①control group received sham operation ; ②ischemia reperfusion (I - R) group received a occlusion and open up of left anterior desending( LAD) ; ③nicotine 400 μg/kg group were intraperitoneal injected with nicotine 30 minutes before performing an operation; ④nicotine 200 μg/kg group; ⑤nicotine 40 μg/kg group. The infarct size of myocardium were measured. The myocardium tissues were collected after operation and histopathological examinations were performed. The contants of tumor necrosis factor - α( TNF - α) and interleukin - 6( IL - 6) of blood were measured by ELISA. Results Compared with I - R group, the infarct size of myocardium were significantly decreased in nicotine 400 μg/kg group (P < 0. 01). Compared with I - R group, the histology changes of myocardium tissues were significantly alleviated in nicotine 400 μg/kg group. Nicotine significantly suppressed TNF - α and IL - 6 production in myocardium ischemia reperfusion rat. Conclusion Nicotine can significantly decrease the infarct size of myocardium, alleviate the injury changes of myocardium , and reduce the release of TNF - α and IL - 6 in myocardium ischemia reperfusion rat. Nicotine have a proleclive effect against myocardium ischemia reperfusion by cholinergic anti - inflammatory path-way.