去肾交感神经术对心肌梗死后犬心脏氧化应激和交感神经重构的影响

Effect of renal denervation on cardiac oxidative stress and sympathetic nerve remodeling after myocardial infarction in canine

目的观察去肾交感神经术(RDN)对犬心肌梗死(MI)后心脏氧化应激和交感神经重构的影响。方法将18只健康犬随机分为3组:假手术组6只,只行冠脉造影检查;心肌梗死组(MI组)6只,建立MI模型后1周行肾动脉造影检查;心肌梗死+RDN治疗组(MI+RDN组)6只,建立MI模型后1周行RDN治疗。明胶海绵栓塞法制作MI模型后4周,通过超声心动图测量各组犬左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)、左室射血分数(LVEF);免疫组化法检测梗死周边区酪氨酸羟化酶(TH)阳性神经纤维分布和密度;检测心肌氧化应激指标:超氧化物歧化酶(SOD)、丙二醛(MDA)含量。结果与假手术组相比,MI组和MI+RDN组LVEF和SOD降低(P<0.05),LVEDV、LVESV、MDA和TH阳性神经纤维相对表达量均增加(P<0.05)。TH阳性神经纤维相对表达量与SOD呈负相关(rs=-0.818,P<0.05),与MDA呈正相关(rs=0.900,P<0.05)。MI+RDN组较MI组LVEF和SOD升高(P<0.05),而LVEDV、LVESV、MDA和TH阳性神经纤维相对表达量均降低(P<0.05)。结论 RDN可以降低心脏氧化应激水平、抑制MI后心脏交感神经重构、改善心功能。

Objective To observe the effect of renal denervation （RDN） on the cardiac oxidative stress and sympathetic nerve remodeling after myocardial infarction （MI） in canine. Methods Canine （n=18） were randomly divided into three groups： Sham operation group （SHAM group, n=6）, MI group （n=6）, MI＋RDN group （n=6）. Anterior myocardial inthrction was gained by gelatin sponge embolization of the left anterior descending artery. At four weeks post-MI, left ventricular end- diastolic volume （LVEDV）, left ventricular end-systolic volume （LVESV） and left ventricular ejection fraction （LVEF） were examined using echocardiography. Immunohistochemical assay was used to analyze the distribution and density of tyrosine hydroxylase （TH） stained nerve fibers at peri-infarct zone. Myocardial superoxide dismutase （SOD） activity and malondialde- hyde （MDA） were also assessed. Results Compared with dogs in SHAM group, LVEF and SOD expression were decreased in MI group and MI＋RDN group （P 〈 0.05）, but Left ventricular end diastolic pressure （LVEDP）, LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were increased （P 〈 0.05）. There was a negative correlation between the rate of TH positive staining nerve fibers and SOD level （r=-0.818 ,P 〈 0.05） and a positive correlation between rate of TH positive staining nerve fibers with MDA level （r=0.900, P 〈 0.05）. By contract, compared with MI group, LVEF and SOD in MI ＋ RDN group were increased （P 〈 0.05）, while LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were significantly lowered （P 〈 0.05）. Conclusion RDN is effective to decrease the level of cardiac oxidative stress and improve cardiac sympathetic nerve remodeling and heart function after myocardial infarction in canine.