肾脏去神经联合美托洛尔对自发性高血压大鼠的血压和心脏肥厚的作用

The role of renal denervation combined with metoprolol on cardiac hypertrophy and blood pressure in Spontaneous hypertensive rats

目的:研究经腹肾脏去神经联合常用β-肾上腺受体阻断药美托洛尔对高血压大鼠的降压疗效及其对心脏肥厚的作用。方法:以12周雄性自发性高血压大鼠(spontaneous hypertension rat,SHR)为研究对象,分为假手术组(A组)和手术组,而手术组在术后随机分为双侧肾动脉去神经组+空白药物对照组(B组)、双侧肾动脉去神经+美托洛尔组(C组)。术后及联用药物后第2、4、6周,探测SHR尾动脉压、心率和心脏超声;第6周,检测心脏组织肥厚基因的表达、测定左室质量指数(left ventricular mass index,LVMI)和行组织病理切片HE染色。结果:各组SHR术后心率比较差异无统计学意义(P>0.05),而联用药物后2、4、6周,C组比A组和B组心率减慢,差异有统计学意义(P<0.05);与A组比较,术后联用药物2周B组、C组血压开始降低,并随时间推移而持续下降(P<0.05);而与B组比较,C组更明显。与A组比较,术后联用药物4周,B组、C组的左室壁厚度开始出现差异,且C组差异更明显(P<0.05)。心脏组织的病理切片和肥厚基因表达变化显示,术后联用药物6周,与A组比较,B组及C组的心脏体积减小、室壁变薄、肥厚相关基因β-MHC和ANP表达下降,差异有统计学意义(P<0.05),同时左室质量指数显示同样的结果。结论:肾脏去神经可以降低成年SHR的血压和减轻心脏肥厚,而联合美托洛尔其效果更显著。

Objective：To explore the effects of renal denervation combined withβ-adrenergic receptor blocker drugs（metoprolol）on blood pressure and cardiac hypertrophy in spontaneous hypertensive rats.Method：Male Sprague-Dawley rats were divided into the sham-operated group（A group）and operated group.The operated rats were served as bilateral renal artery denervation combined with blank drug control（B group）and metoprolol treatment（C group）.At 0,2,4,6weeks postsurgery combined with drugs treatment,transthoracic two-dimensinonally guided M-mode echocardiogrophy was performed,heart rates were measured and blood pressures were acquired with exploring rat tail arterial pressure.At 6weeks postsurgery combined with drugs treatment,the expression of hypertrophy-related gene was detected,left ventricular mass index was calculated and histological sections were stained with hematoxylin and eosin（HE）.Result：Heart rates were not various in different groups after postsurgery,while the heart rates of C group were more significantly reduced at2,4,6weeks after combined with metoprolol,compared with A group and B group（P〈0.05）;compared to A group,the blood pressure was gradually decreased in B group and C group from two weeks after combined with drug（p0.05）;At two weeks,it was more outstanding in C group,compared with B group;At 4weeks after combined with drug,the thickness of left ventricular was alleviated in B group and C group in comparison with A group,but C group was more notable.The result of histological sections and hypertrophy-related gene expression declared that at 4weeks after combined with drug,compared with A group,all of the volume of heart,the thickness of left ventricular and the expression of hypertrophy-related gene（β-MHC and ANP）were reduced in B group and C group.Moreover,the data of left ventricular mass index showed similar results.Conculsion：Renal denervation therapy can reduce blood pressure and alleviate cardiac hypertrophy of spontaneous hypertensive rats,but combined with metoprolol was more significant.