目的:探讨钾通道开放剂尼可地尔对离体大鼠心肌缺血再灌注损伤(MIRI)的影响。方法:建立Langendorff离体心脏灌流系统,44只大鼠随机分为4组:正常组、缺血再灌注组(I-R组)、腺苷(100μmol/L)缺血再灌注组(A/I-R组)、尼可地尔(200μmol/L)缺血再灌注组(N/I-R组),每组11只。分别记录并分析各组左心室发展压(LVDP)、左心室内压力最大上升/下降速率(±dp/dt_(max))、再灌注心律失常(RA)、心肌梗死面积以及左心室心肌组织的乙醛脱氢酶2(ALDH2)、抗凋亡基因B淋巴细胞瘤-2(Bcl-2)以及促凋亡基因B淋巴细胞瘤-2相关x蛋白(Bax)的表达水平。结果(:1)N/I-R组再灌注30 min与再灌注45 min的LVDP均高于I-R组与A/I-R组(P均〈0.05)。(2)I-R组再灌注30 min及45 min的±dp/dt_(max)均低于N/I-R组和A/I-R组(P均〈0.05)。N/I-R组再灌注30 min及45 min的±dp/dtmax均高于A/I-R组(P均〈0.05)。(3)与I-R组比较,N/I-R组和A/I-R组的RA评分均降低(P均〈0.01)。N/I-R组与A/I-R组差异无统计学意义(P=0.771)。(4)N/I-R组和A/I-R组心肌梗死面积均低于I-R组(P均〈0.01),N/I-R组心肌梗死面积最小(P〈0.05)。(5)与正常组比较,I-R组线粒体ALDH2表达明显减少,Bcl-2、Bax的表达增加;N/I-R组线粒体ALDH2表达增加,A/I-R组表达减少,N/I-R组和A/I-R组的Bcl-2、Bax的表达均增加。与I-R组比较,N/I-R组以及A/I-R组Bcl-2/Bax的比值均增大(P均〈0.05);在抗凋亡方面N/I-R组与A/I-R组差异无统计学意义(P〉0.05)。结论:尼可地尔可以减少MIRI,对心肌起到保护作用,其总体作用效果优于腺苷。尼可地尔可上调线粒体ALDH2、Bcl-2表达以及下调Bax的基因蛋白的表达。
Objective: To investigate the effect of potassium channel opener nicorandil on myocardial ischemia-reperfusion injury(MIRI) in isolated rat's heart. Methods: Langendorff system was established for isolated heart reperfusion. A total of 44 rats were randomly divided into 4 groups: Normal control group, Ischemia-reperfusion(I-R) group, Adenosine/I-R(A/I-R) group, the I-R heart was treated by adenosine 100 μmo/L and Nicorandil/I-R(N/I-R) group, the I-R heart was treated by nicorandil 200 μmo/L. n=11 in each group. Left ventricular developed pressure(LVDP), the maximal rise/fall rate of left ventricular pressure(±dp/dtmax), reperfusion arrhythmia(RA) and myocardial infarction(MI) size were recorded; the expressions of left ventricular tissue acetaldehyde dehydrogenase 2(ALDH2), Bcl-2 and Bax were examined and compared among different groups.Results:(1) Compared with I-R and A/I-R groups, N/I-R group had increased LVDP at 30 min and 45 min reperfusion, all P 0.05.(2) Compared with N/I-R and A/I-R groups, I-R group showed reduced ±dp/dtmax at 30 min and 45 min reperfusion, all P〈0.05; while ±dp/dtmax in N/I-R group was higher than A/I-R group at 30 min and 45 min reperfusion, all P〈0.05.(3) Compared with I-R group, both N/I-R and A/I-R groups presented reduced RA score, all P〈0.01, RA score wassimilar between N/I-R group and A/I-R group, P=0.771.(4) compared with I-R group, both N/I-R and A/I-R groups had the smaller MI size, P〈0.01 and N/I-R group showed the smaller MI size, P〈0.05.(5) Compared with Normal control group, I-R group had decreased mitochondrial ALDH2 expression and increased Bcl-2, Bax expression; ALDH2 level was elevated in N/I-R group had reduced in A/I-R group; Bcl-2 and Bax levels were increased in both N/I-R and A/I-R groups. Compared with I-R group, both N/I-R and A/I-R groups had increased ratio of Bcl-2/Bax, P〈0.05; the anti-apoptosis effect was similar between N/I-R group and A/I-R group, P〈0.05. Conclusion: N