【摘要】 目的探讨地尔硫?对离体大鼠心肌缺血再灌注损伤的影响及其机制。方法 33只大鼠随机分为3组:正常对照组(N组)、缺血再灌注组(I-R组)、地尔硫?+缺血再灌注组(D/I-R组)。N组持续灌流K-H液150 min;I-R组K-H液稳定灌流30 min后,结扎前降支30 min,继以K-H液再灌注90 min;D/I-R组给予地尔硫?(5μmo/L)再灌注15 min,继以K-H液再灌流75 min。记录并分析各组大鼠左心室发展压、左心室内压力最大上升/下降速率(±dp/dtmax)、再灌注心律失常评分、心肌梗死面积以及各组左心室心尖组织的线粒体乙醛脱氢酶2(ALDH2)、Bcl-2以及Bax的m RNA基因与蛋白表达水平。结果 (1)左心室发展压D/I-R组再灌注30 min与45 min比I-R组压力明显升高[(92.68±5.09)mmHg vs(75.77±5.33)mmHg;(90.39±4.29)mmHg vs(72.34±7.49)mmHg;1 mmHg=0.133 kPa],差异均具有统计学意义(F=72.81、51.92,P均=0.001)。(2)±dp/dtmax D/I-R组再灌注30 min与45 min时均比I-R组升高[+dp/dtmax:(2885.45±286.47)mmHgvs(2063.64±105.57)mmHg;(2712.73±236.52)mmHgvs(2053.64±92.33)mmHg;-dp/dtmax:(2214.55±104.63)mmHgvs(1710.91±217.97)mmHg;(2119.09±84.43)mmHg vs(1544.55±207.72)mmHg],差异均具有统计学意义(F=64.22、70.55、69.77、54.64,P均=0.001)。(3)N组仅有室性期前收缩的发生,未发生心室颤动、室性心动过速;D/I-R组出现室性期前收缩的个数较N组增加,差异具有统计学意义(P=0.001);I-R组室性心动过速发生率高于D/I-R组,心室颤动时程与室性心动过速时程均较D/I-R组增加,差异具有统计学意义(P=0.013、0.049、0.001);再灌注心律失常评分I-R组评分[5(3,6),57.36]高于D/I-R组[3(1,4),34.77],差异具有统计学意义(P=0.001)。(4)心肌梗死面积I-R组高于D/I-R组[(55.51±1.43)%vs (17.01±1.13)%],差异具有统计学意义(P <0.01)。(5)I-R组线粒体ALDH2表达明显减少。D/I-R组线粒体ALDH2表达与I-R组比较减少,但差异无统计学意义(P=0.11),Bcl-2、Bax的表达均增加,D/I-R组Bcl-2/Bax的比值较I-R组增大(0.44 vs 0.22),差异具有统计学意义(P=0.001)。结论地尔硫?处理后能够减少缺血再灌注损伤。其保护作用机制之一可能是通过上调Bcl-2下调Bax的基因和蛋白表达,减少心肌细胞的凋亡,但其并不是通过上调线粒体ALDH2的基因与蛋白来实现。更多还原

【Abstract】 Objective To investigate the effects of diltiazem on myocardial ischemia-reperfusion injury(MIRI) and the underlying mechanisms. Methods Wistar rats were randomly divided into three groups: normal group(N group), ischemia-reperfusion group(I-R group), diltiazem + ischemia-reperfusion group(D/I-R group). The isolated rat hearts in different groups were given different perfusion treatments: The N group was given continuous perfusion of K-H liquid for 150 min; the I-R group was given stable perfusion of K-H liquid for 30 min followed by ligating the left anterior descending coronary artery for 30 min, and K-H liquid reperfusion for 90 min; the D/I-R group underwent reperfusion with diltiazem(5 μmo/L) for 15 min and reperfusion with K-H liquid for 75 min. Left ventricular cardiac function(LVDP), maximal rise/fall rate of left ventricular pressure(±dp/dtmax), reperfusion arrhythmia(RA) score, calculated myocardial infarct(MI) size, and ALDH2, Bcl-2, and BAX expression in the left ventricular apex were recorded in each group. Results The LVDP at 30 min and 45 min in the D/I-R group was significantly higher than that of the I-R group, respectively [(92.68±5.09) mmHg vs(75.77±5.33) mmHg, F=72.81, P=0.001;(90.39±4.29) mmHg vs(72.34±7.49) mmHg, F=51.92, P=0.001]. The ±dp/dtmax at 30 min and 45 min in the D/I-R group were significantly higher than that of the I-R group, respectively [ + dp/dtmax:(2885.45±286.47) mmHg vs(2063.64±105.57) mmHg, F=64.22, P=0.001 and(2712.73±236.52) mmHg vs(2053.64±92.33) mmHg, F=70.55, P=0.001;-dp/dtmax:(2214.55±104.63) mmHg vs(1710.91±217.97) mmHg, F=69.77, P=0.001 and(2119.09±84.43) mmHg vs(1544.55±207.72) mmHg, F=54.64, P=0.001, respectively]. The number of ventricular pre-contractions in the I-R group was significantly higher than that of the D/I-R group(P=0.001). The incidence of ventricular tachycardia, the time history of ventricular fibrillation, and the duration of ventricular tachycardia in the I-R group were also significantly higher than those of the D/I-R group(P=0.013, 0.049, and 0.001, respectively). The reperfusion arrhythmia score in the I-R group [5(3, 6), 57.36] was significantly higher than that of the D/I-R group [3(1, 4), 34.77](P=0.001). Compared with the I-R group, the D/IR group had significantly smaller MI size [(55.51±1.43)% vs(17.01±1.13)%, P < 0.01]. In the I-R group, the expression of mitochondrial ALDH2 was significantly reduced and that of Bcl-2 and Bax increased. Compared with the I-R group, the expression of mitochondrial ALDH2 was not significantly decreased in the D/IR group(P=0.11), while the expression of Bcl-2 and Bax was significantly increased. Compared with the I-R group, the D/I-R group had significantly increased Bcl-2/Bax ratio(0.44 vs 0.22, P=0.001). Conclusion Diltiazem reduces MIRI possibly by up-regulating the expression of mitochondrial Bcl-2 and down-regulating the expression of Bax. However, the therapeutic effect of diltiazem is not related with the gene and protein expression of mitochondrial ALDH2.更多还原