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

Experimental study of nicotine against myocardium ischemia - reperfusion injury in rat by cho-linergic anti - inflammatory pathway

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-蛞组、烟碱200彬ks组和烟碱40μg／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-仪（TNF—Ot）和白细胞介素-6（IL-6）水平。结果与缺血再灌注组比较，烟碱400μg∥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400μg／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4h血浆TNF—q水平明显高于对照组（P〈0．01）；烟碱400μg／kg组4h血浆TNF-0l水平、200I．Lg／kg组和40斗g／kg组均明显低于缺血再灌注组（P〈0．01）。缺血再灌注组大鼠4h血浆IL-6水平明显高于对照组（P〈0．01）。烟碱400μg／kg组和200μ∥kg组4h血浆IL-6水平均明显低于缺血再灌注组（P〈0．01）。烟碱400pg／kg组与40μg／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 by 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 reperfu- sion （I -R）group received a occlusion and open up of left anterior desending（LAD） ; ③nicotine 400μg/kg group were intraperitoneal injected with nicotine 30 minutes before performing an operation; ④nieotine 200 txg/kg group; ⑤nieotine 40 μg/kg group. The infarct size of myoeardium were meas- ured. The myoeardium tissues were collected after operation and histopathological examinations were per- formed. The contants of tumor necrosis factor - a （ TNF - et） and interleukin - 6 （ IL - 6 ） of blood were measured by ELISA. Results Compared with I - R group, the infarct size of myoeardium were signifi- candy 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 signif- icantly suppressed TNF -aand IL- 6 production in myocardium ischemia reperfusion rat. Conclusion Nicotine can significantly decrease the infarct size of myocardium, alleviate the injury changes of myo- eardium, and reduce the release of TNF - a and IL - 6 in myocardium ischemia reperfusion rat. Nicotinehave a protective effect against myocardium ischemia reperfusion by eholinergic anti - inflammatory path- way.