药物后处理对离体大鼠心肌缺血再灌注损伤影响的对比研究Comparative study of the effect of different drugs on post-conditioning of myocardial ischemia reperfusion injury on isolated rat heart models
张云盛,滕天明,康毅,崔健,夏钊,张文娟
摘要(Abstract):
目的观察治疗浓度的硝酸甘油、地尔硫艹卓、尼可地尔以及腺苷对离体大鼠心肌缺血再灌注损伤的影响,探讨四种药物发挥心肌保护作用的不同机制以及各个药物的相对优劣。方法66只大鼠随机分为六组:正常对照组(N组)、缺血再灌注组(I-R组)、硝酸甘油组、地尔硫艹卓组、尼可地尔组、腺苷组。N组持续灌流Krebs-Henseleit液(K-H液)150 min;I-R组稳定灌流K-H液30 min后,结扎前降支30 min,继以K-H液再灌注90 min;药物后处理组分别在再灌注即刻给予硝酸甘油(10-8mol/L)、地尔硫艹卓(5μmo/L)、尼可地尔(200μmo/L)以及腺苷(100μmo/L)再灌注15 min,继以K-H液灌流75 min。记录并分析各组左心室发展压(left ventricular developed pressure,LVDP)、左心室内压力最大上升/下降速率(±dp/dtmax)、再灌注心律失常(RA)评分以及心肌梗死面积(myocardial infarct size)。结果 (1)I-R组再灌注30 min及45 min时LVDP均低于各药物后处理组(均P<0.05)。在药物后处理组,再灌注30 min地尔硫艹卓组LVDP[(92.68±5.09)mm Hg比(84.26±3.02)mm Hg比(83.35±2.88)mm Hg]、尼可地尔组LVDP[(88.95±1.75)mm Hg比(84.26±3.02)mm Hg比(83.35±2.88)mm Hg],再灌注45 min地尔硫艹卓组LVDP[(90.39±4.29)mm Hg比(82.09±4.24)mm Hg比(80.98±3.89)mm Hg]、尼可地尔组LVDP[(86.13±2.38)mm Hg比(82.09±4.24)mm Hg比(80.98±3.89)mm Hg]均高于硝酸甘油组与腺苷组,且地尔硫艹卓组高于尼可地尔组,差异均有统计学意义(均P<0.05),但硝酸甘油组与腺苷组比较,差异均无统计学意义(均P>0.05)。(2)I-R组再灌注30 min及45 min的±dp/dtmax均低于各药物后处理组(均P<0.05)。地尔硫艹卓组、尼可地尔组再灌注30 min及45 min的±dp/dtmax均高于硝酸甘油组、腺苷组,且地尔硫艹卓组高于尼可地尔组,差异均有统计学意义(均P<0.05)。但硝酸甘油组与腺苷组比较,差异无统计学意义(P>0.05)。(3)RA评分比较:I-R组评分[5(3,6),57.36]明显高于尼可地尔组[1(1,3),22.05]、地尔硫艹卓组[3(1,4),34.77]、硝酸甘油组[4(1,4),45.41]和腺苷组[2(1,3),23.14],差异均有统计学意义(均P<0.05)。尼可地尔组RA评分最低,但尼可地尔组与腺苷组差异无统计学意义(P=0.771)。(4)心肌梗死面积比较:硝酸甘油组(27.04±2.45)%、地尔硫艹卓组(17.01±1.13)%、腺苷组(47.97±1.22)%以及尼可地尔组(34.95±1.25)%均小于I-R组(55.51±1.43)%,差异均有统计学意义(均P<0.01)。各药物后处理组组间比较差异均有统计学意义(均P<0.01),且地尔硫艹卓组梗死面积最小。结论硝酸甘油、地尔硫艹卓、尼可地尔以及腺苷药物后处理均可以减少心肌缺血再灌注损伤,对缺血心肌起到保护作用。其中,地尔硫艹卓在改善心脏泵功能以及减少心肌梗死面积方面效果最好;在药物后处理RA评分方面,尼可地尔和腺苷效果更好。
关键词(KeyWords): 药物后处理;缺血再灌注损伤;硝酸甘油;地尔硫艹卓;尼可地尔;腺苷
基金项目(Foundation): 天津市高等学校科技发展基金计划项目(20110151)
作者(Author): 张云盛,滕天明,康毅,崔健,夏钊,张文娟
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