肾血管性高血压大鼠外周血管生成素2的变化及替米沙坦的干预作用

Variation of serum angiopoietin-2 in renovascular hypertensive rats and therapeutic effect of telmisartan

目的:研究血管生成素-2(angiopoietin-2,Ang-2)在肾血管性高血压及心肌肥厚进展中的作用,并探讨替米沙坦对肾血管性高血压、心肌肥厚、心脏功能及外周Ang-2水平的影响。方法:清洁级雄性SD大鼠24只,随机分为对照组、假手术组、两肾一夹(two-kidney one clip,2K1C)组和2K1C+替米沙坦组。2K1C组及2K1C+替米沙坦组采用2K1C方法制备高血压模型,其中2K1C+替米沙坦组每天以替米沙坦10mg/kg灌胃干预,2K1C组采用等量蒸馏水灌胃。分别于术前及术后经动脉插管测血压,8周时以超声心动图检测心脏结构及功能变化,随后处死大鼠,取外周动脉血清以ELISA方法检测Ang-2水平。结果:(1)与对照组、假手术组相比,2K1C组血压显著升高、心肌肥厚明显(P<0.01);2K1C+替米沙坦组血压较2K1C组明显降低,心肌肥厚亦明显减轻(P<0.01);(2)与对照组、假手术组相比,2K1C组动脉血清Ang-2水平明显升高(P<0.01),且与血压水平、心肌肥厚程度呈正相关;2K1C+替米沙坦组Ang-2水平与2K1C组差异无统计学意义(P>0.05)。结论:Ang-2在肾血管性高血压外周动脉血清中表达增加,且与心肌肥厚相关;替米沙坦可显著降低肾血管性高血压大鼠的血压、抑制心肌肥厚,对外周血清Ang-2水平无明显影响,提示替米沙坦降压机制可能与Ang-2无关。

Objective：To study the effects of angiopoietin-2 in the development of hypertension and myocardial hypertrophy, and further to explore the effects of telmisartan on the myocardial hypertrophy and blood pressure in two kidney one clip （2K1C） hypertensive rats. Methods：24 Male Sprague-Dawly rats were randomly divided into control group （n = 6）, sham operation group （n = 6）, 2 kidney 1 clip （2K1C） group （77：6） and 2KIC＋ telmisartan group（n =6）. 2K1C hypertensive model was established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. Before and eight weeks after the operation, blood pressure was measured by arterial catheterization, the myocardial structure and function were detected by ultrasonography, and the serum angiopoietin-2 was evaluated by ELISA. Results： Eight weeks later, blood pressure and the thickness of left ventricle in 2K1C group were significantly higher than those in control and sham groups （P〈0.01, respectively）. Compared with those in 2K1C group, blood pressure and thickness of left ventricle in 2K1C ＋ telmisartan group were significantly decreased （P〈0.01, respectively）. Serum level of angiopoietin-2 was statistically increased in 2K1C group and was closely related to blood pressure and extent of myocardial hypertrophy, but was not decreased in 2K1C ＋ telmisartan group（P〉0.05）. Conclusion：Serum level of Angiopoietin 2 is increased in the renovaseular hypertensive rats, and is positively related to myocardial hypertrophy. Telmisartan can reduce blood pressure and prevent myocardial hypertrophy, but can not decrease the angiopoietin-2 level, which indicates that it maybe not be associated with angiopoietin-2 level for telmisartan to prevent myocardial hypertrophy.