地昔帕明对心肌缺血后交感神经重构和室颤阈值的影响

Effect of desipramine on sympathetic remodeling and ventricular fibrillation threshold after myocardial ischemia

目的:研究地昔帕明对大鼠急性心肌缺血后交感神经重构和室颤阈值的影响,并探讨交感神经重构与室颤阈值的关系。方法:将60只SD大鼠随机分为3组,每组各20只:即心肌缺血组:夹闭左冠状动脉前降支30 min;地昔帕明组:先单次静脉给予地昔帕明0.8 mg/kg,5 min后夹闭左冠状动脉前降支30 min及假手术组:仅开胸但不夹闭左冠状动脉。喂养1周后,开胸测定室颤阈值。用免疫组化染色法检测大鼠心室肌中生长相关蛋白43(GAP43)和酪氨酸羟化酶(TH)阳性神经纤维的分布和密度,并用RT-PCR测定梗死周边区GAP43和THmRNA表达的水平。结果:地昔帕明组的室颤阈值(11.0±2.65)V较心肌缺血组(7.2±1.30)V显著增高(P<0.05);与假手术组的(13.0±2.12)V比较无明显差异。心肌缺血组GAP43和TH阳性神经纤维的分布紊乱,密度明显高于地昔帕明组和假手术组(P<0.05)。与心肌缺血组相比,地昔帕明组GAP43和TH mRNA表达的水平显著降低(P<0.05)。结论:地昔帕明可改善心肌缺血后交感神经重构,提高室颤阈值,增加缺血心脏的电稳定性。

AIM： To investigate whether desipramine can modulate sympathetic remodeling and ventricular fibrillation threshold （VFT） in rats with induced acute myocardial ischemia and to study the relationship between sympathetic remodeling and VFT. METHODS： Sixty Sprague Dawley rats were randomly assigned into three groups. In the myocardial ischemia group, the left anterior descending coronary artery （LAD） was clamped for 30 rain. In the desipramine group, 5 min prior to clamping, desipramine （0. 8 mg/kg） was administered IV. In the sham-operated group, operation was performed on rats but without clamping the coronary artery. One week after the operation, VFT was measured and the distribution and density of growth-associated protein43 （ GAP43 ） and tyrosine hydroxylase （TH） -positive nerve fibers in ventricle were detected by immunohistochemical techniques. GAP43 and TH mRNA expression levels in infarcted border zone were also measured by RT-PCR techniques. RESULTS ： VFT of desipramine group （ 11.0±2.65 ） V was significantly higher than that in myocardial ischemia group （7.2±1.30 ） V （ P 〈 0. 05）, but no significant difference was found compared with that in sham-operated group （13. 0±2. 12） V. The distribution of nerve fibers in myocardial ischemia group was chaotic and the density was significantly higher than in the desipramine group and sham-operated group （P 〈 0.05 ）. Compared with those in myocardial ischemia group, GAP43 and TH mRNA expression levels in desipramine group decreased significantly （ P 〈 0. 05 ）. CONCLUSION ： Desipramine improves sympathetic remodeling and increases VFT and electrical stability of ischemic hearts after acute myocardial ischemia.