烟碱激活胆碱能抗炎通路治疗心肌缺血再灌注损伤的实验研究

Experimental Study of Nicotine Against Myocardium Isehemia Reperfusion Injury in Rat by Cholinergic Anti-inflammatory Pathway

目的探讨烟碱对心肌缺血/再灌注损伤的保护作用。方法采用左冠状动脉前降支结扎-开放法建立大鼠心肌缺血再灌注损伤动物模型。30只大鼠随机分为对照组(假手术组)、缺血再灌注组、烟碱400μg/kg组、烟碱200μg/kg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、主要器官组织病理学,动脉血乳酸盐测定和血气分析。结果与缺血/再灌注组心肌细胞梗死面积(47.72±9.77)%相比,烟碱400μg/kg组(32.26±10.44)%,差异具有显著性(P<0.01)。与缺血/再灌注组动脉血pH值(7.13±0.05)相比,烟碱400μg/kg组(7.41±0.06)、200μg/kg组(7.41±0.08)、40μg/kg组(7.33±0.16)差异均有统计学意义(P均<0.01)。与缺血/再灌注组动脉血BE值(-15.17±4.49)mmol/L相比,烟碱400μg/kg组(-1.00±3.16)、200μg/kg组(-1.00±4.00)和40μg/kg组(-4.50±6.02)差异均有统计学意义(P均<0.01)。与缺血/再灌注组动脉血乳酸盐浓度(5.92±1.66)mmol/L相比,烟碱400μg/kg组(1.28±0.85)、200μg/kg组(1.28±0.85)和40μg/kg组(2.87±0.72)差异均有统计学意义(P均<0.05),并且烟碱400μg/kg组与40μg/kg组之间差异有显著性(P<0.05)。病理学检查:缺血/再灌注组心肌组织可见多处散在坏死灶,大片心肌细胞坏死,坏死处原有心肌结构消失,大量炎性细胞浸润。烟碱400μg/kg组可见散在一些坏死灶,未见大片坏死细胞。缺血/再灌注组肝细胞肿胀、空泡样脂肪变性,点状或小片状坏死。肝脏门管区局灶性脓肿,肝血窦扩张,中性粒细胞浸润于血管壁。烟碱400μg/kg组肝细胞浊肿,轻度脂肪变性,未见明显坏死灶。肝血窦中中性粒细胞浸润较轻。缺血/再灌注组部分肺泡上皮细胞肿胀,肺泡隔增宽,毛细血管明显扩张瘀血,微血栓形成,肺间质充血水肿,弥漫性中性粒细胞浸润,肺泡腔变小,部分区域肺萎缩,肺泡腔内大量炎性渗出。烟碱400μg/kg组小血管及毛细血管内中性粒细胞浸润较轻,肺间质轻度水肿,肺泡隔增宽不明显,肺泡腔无渗出物。结论烟碱作用于心肌缺血再灌注损伤大鼠后,明显减轻心肌细胞损伤,减小缺血面积;对肝、肺组织具有保护作用;降低动脉血乳酸盐浓度,稳定细胞外液碱剩余和血液酸碱度。

Objective To investigate the protective effect of nicotine activing cholinergic anti-inflammatory pathway on myocardium isehemia reperfusion injury in rat. Methods 30 rats were randomly divided into 5 groups, each group 6 rats.①control group received sham operation ; ②isehemia reperfusion （1-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;④nicotine 200μg/kg group; ⑤nicotine 40μg/kg group. The infarct size of myocardium were measured. The myocardium tissues, liver tissues and lung tissues were collected after operation and histopathologieal examinations were performed. The contant of lactic acid and blood gas of artery were measured. Results Compared with I-R group, the infarct size of myocardium and lactic acid content of artery blood were significantly decreased, as well as the pH and BE of artery blood were remarkedly increased in nicotine 400μg/kg group （P〈0.01）.Compared with control group, there were obvious histopathological changes in myocardium tissues, hepatic tissues and lung tissues in I-R group. Compared with I-R group, the histology changes of myocardium tissues, hepatic tissues and lung tissues were significantly alleviated in nicotine 400μg/kg group. Couclusiou Nicotine can significantly decrease the infarct size of myocardium, alleviate the injury changes of liver and lung, ameliorate the pH, BE and lactic acid content of artery blood in myocardium isehemia reperfusion rat. Nicotine have a protective effect against myocardium isehemia reperfusion.