辛伐他汀对大鼠心肌梗死后心房神经重构和电重构的影响

Effects of simvastatin on neural and electrical remodeling of atria in rats with myocardial infarction

目的探讨辛伐他汀对大鼠心肌梗死后心房神经重构和电重构的影响。方法将建立心肌梗死模型成功的22只SD大鼠随机分为心肌梗死组(n=11)和辛伐他汀组(n=11);另设假手术组(n=11):在大鼠心脏的相同部位只穿线不结扎。4周后,对大鼠行超声心动图和心房电生理检查;免疫组织化学法检测生长相关蛋白-43(GAP-43)和酪氨酸羟化酶(TH)阳性神经纤维的分布和密度;Real-Time PCR法检测神经生长因子(NGF)mRNA的表达。结果与假手术组比较,心肌梗死组NGF mRNA表达升高、阳性神经纤维密度增加、左心房内径增大、射血分数降低,并伴随心房有效不应期(AERP)缩短及房性快速心律失常(AT)诱发率升高,差异均有统计学意义(P<0.05)。与心肌梗死组比较,辛伐他汀组NGF mRNA表达降低、阳性神经纤维密度减少、左心房内径减小、射血分数升高,并伴随AERP延长及AT诱发率降低,差异也有统计学意义(P<0.05)。但辛伐他汀组仍不能使上述指标恢复到假手术组水平,差异有统计学意义(P<0.05)。结论辛伐他汀通过改善大鼠心肌梗死后心房神经重构及电重构而起到预防AT的作用,其机制可能与NGF表达下调有关。

Objective To investigate the effects of simvastatin on neural and electrical remodeling of atria in rats with myocardial infarction.Methods Twenty-two SD rats were randomly divided into myocardial infarction group（n=11） and simvastatin group（n=11） after successful establishment of model of myocardial infarction,and another 11 rats were served as sham operation group which were not ligated in the same part of the heart.Four weeks after operation,echocardiographic and electrophysiologic examinations were conducted,immunohistochemistry was used to determine the distribution and density of growth-associated protein-43（GAP-43） and tyrosine hydroxylase（TH） positive staining nerve fibers,and expression of nerve growth factor（NGF） mRNA was detected by Real-Time PCR.Results Compared with sham operation group,the expression of NGF mRNA and density of positive staining nerve fibers were significantly higher,the diameter of left atria was much longer,the ejection fraction was significantly lower,the atrial effective refractory period（AERP） was much shorter,and the prevalence of atrial tachyarrhythmia（AT） was significantly higher in myocardial infarction group（P0.05 for all）.Compared with myocardial infarction group,the expression of NGF mRNA and density of positive staining nerve fibers were significantly lower,the diameter of left atria was much shorter,the ejection fraction was significantly higher,AERP was much longer,and the prevalence of AT was significantly lower in simvastatin group（P0.05 for all）.However,there were still significant differences in these parameters between simvastatin group and sham operation group（P0.05）.Conclusion Simvastatin can effectively improve neural and electrical remodeling of atria in rats with myocardial infarction,and may play a potential role in the prevention of AT,the mechanism of which may be associated with the down-regulation of expression of NGF.