摘要目的 评价烟碱预先给药对心肌缺血再灌注大鼠心功能的影响.方法 健康成年雄性SD大鼠60只,体重200 ～ 250 g,采用随机数字表法,将其分为3组(n=20)∶假手术组(S组)、心肌缺血再灌注组(IR组)和烟碱预先给药组(N组).S组丝线穿过冠状动脉前降支但不结扎；IR组采用丝线结扎左冠状动脉前降支30 min后再灌注120 min的方法制备大鼠心肌缺血再灌注模型.N组结扎前30 min,经右颈静脉注射烟碱400μg/kg,余操作同IR组,S组和IR组右颈静脉注射等量生理盐水.各组随机取10只大鼠于缺血前(T0)、缺血30 min(T1)和再灌注30 min(T2)、120 min(T3)时经生物机能实验系统记录左心室收缩压(LVSP)、左心室舒张压(LVDP)、左室内压上升/下降最大变化速率(±dp/dtmax)、HR和MAP.各组其余10只大鼠于再灌注60 min时采集右颈动脉血样,采用ELISA法测定血浆肌酸激酶同工酶(CK-MB)活性、心肌肌钙蛋白I(cTnI)和TNF-α浓度.结果 与S组比较,IR组T23时MAP和LVSP、T13时HR、LVDP和±dp/dtmax降低,血浆CK-MB活性、cTnI和TNF-α浓度升高,N组T1-2时LVDP、T1-3时HR和±dp/dtmax降低,血浆CK-MB活性、cTnI和TNF-α浓度升高(P＜0.05)；与IR组比较,N组T3时MAP、HR、LVSP、LVDP和±dp/dtmax升高,血浆CK-MB活性、cTnI和TNF-α浓度降低(P＜0.05).结论 烟碱预先给药通过激活胆碱能抗炎通路,抑制炎性反应,可显著减轻大鼠心肌缺血再灌注损伤,从而改善心功能.

abstractsObjective To evaluate the effect of nicotine pretreatment on cardiac function following myocardial ischemia-reperfusion (I/R) in rats.Methods Sixty male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n =20 each):sham operation group (group S),group I/R and nicotine pretreatment group (group N).The rats were anesthetized with intraperitoneal 20％ urethane 1 g/kg,tracheostomized and mechanically ventilated.Myocardial ischemia was induced by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 120 min of reperfusion.The left anterior descending branch of coronary artery was only exposed,but not occluded in group S.Nicotine 400 μg/kg was injected intravenously via the right jugular vein at 30 min before myocardial ischemia in group N.The equal volume of normal saline was injected instead in groups S and I/R.Before ischemia,at 30 min of ischemia and at 30 and 120 min of reperfusion,10 rats from each group were chosen for record of left ventricular systolic pressure (LVSP),left ventricular diastolic pressure (LVDP),± dp/dtmax,HR and mean arterial pressure (MAP).Blood samples were collected from the right carotid artery of the left 10 rats in each group at 60 min of reperfusion to measure plasma CK-MB activity and cTnI and TNF-α concentrations.Results Compared with group S,MAP and LVSP at T2,3 and HR,LVDP and ± dp/dtmax at T1-3 were significantly decreased,and the plasma CK-MB activity and cTnI and TNF-α concentrations were increased in group I/R,and LVDP at T1,2 and HR and ± dp/dtmax at T1-3 were significantly decreased,and the plasma CK-MB activity and cTnI and TNF-α concentrations were increased in group N (P ＜ 0.05).Compared with group I/R,MAP,HR,LVSP,LVDP and ± dp/dtmax were significantly increased at T3,and the plasma CK-MB activity and cTnI and TNF-α concentrations were decreased in group N (P ＜ 0.05).Conclusion Nicotine pretreatment can reduce myocardial I/R injury through activating cholinergic anti-inflammatory pathway,thus improving cardiac function in rats.