阻断RAAS不同环节对Goldblatt鼠左室重构及细胞凋亡相关蛋白表达的影响

Effect of blocking the different links of RAAS on left ventricular remodeling and the expression of protein about apoptosis in goldblatt rat

[目的]观察缬沙坦及螺内酯阻断RAAS的不同环节对肾血管性高血压大鼠左室重构及细胞凋亡相关蛋白P53、Bax及Bcl-2表达的影响。[方法]5~6周龄SD大鼠56只,随机分为高血压组（n=12,N组）,缬沙坦组（n=11,V组）,螺内酯组（n=12,S组）,缬沙坦及螺内酯组（n=11,S＋V组）,和假手术组（n=10,C组）,V组、S组和S＋V组在左肾动脉置入内径为0.3 mm的银夹（2K1C）,术后第10周行超声心动图检查后,留取左室标本并称重,应用放免法测定心肌组织中的血管紧张素（AngⅡ）、醛固酮（ALD）。应用免疫组化法检测P53、Bax及Bcl-2蛋白的表达。[结果]术后10周N组大鼠血压较C组升高（P〈0.01）。V组和S＋V组血压低于N组（P〈0.05）;心肌组织中AngⅡ和ALD浓度在N组高于C组（P〈0.05）,V组及S＋V组低于N组（P〈0.05）。用药8周后P53在N组中出现阳性表达;Bax与Bcl-2在N组中的表达升高（P〈0.05）,Bcl-2与Bax的比值下降;与N组相比S组Bax与Bcl-2的比值下降（P〈0.05）。V、S＋V组Bax、Bcl-2及Bax与Bcl-2的比值下降,接近C组。[结论]在Goldblatt鼠模型中,压力负荷对左室肥厚（LVH）的形成及细胞凋亡蛋白的过表达起重要的作用。缬沙坦可以明显逆转左室肥厚的发生、改善心功能。螺内酯可以部分地降低血压、逆转左室肥厚,改善心功能。

[ Objective] This study was designed to determined whether blockades of aldosterone receptor with spironolactone and angiotensin Ⅱ receptor with valsartan interfere with the left ventricular（LV） remodeling and the expression of P53, Bax and Bcl - 2 in renovascular hypertension rats. [ Methods ] Two - kidney, one - clip （2K1 C） renovascular hypertension was induced in fifty - six male Sprague - Dawley rats. The rats were randomized to untreated hypertension group （ group N）, spironolactone treatment group （group S）. Valsartan treatment group （group V）, spironolactone and valsartan treatment group （ group S ＋ V）. Ten Sham - operated rats served as the control group （ group C）. After 8 weeks of treatment, the rats were killed and the samples of left ventricle were collected. Left ventricle concentration of angiotensin Ⅱ （Ang） and aldosterone （ALD） were assessed by radioimmunoassay. Immunohistochemistry was adopted to examine the protein expression of P53 ,Bax and Bcl -2. [Results]The blood pressure is higher in N group and S group than V,S ＋ V and C groups（P 〈0.05）. The immunostained positive for P53 protein can be detected in LV in N group but not in S, V, S ＋ V and C group. The levels of Ang in LV of N group were much higher than the other four groups （ P 〈 0.05 ）. The levels of ALD in LV of C group were much lower than the other four groups（ P 〈 0.05 ）, and that of S group was higher than C group. The immunopositivity of Bax in LV in N group was the highest. The Bax/Bcl - 2 protein ratio decreased in N group. Immunopo-sitivity of Bax and the protein ratio in V, S ＋ V group was similar with that in C group. [ Conclusions ] The overload plays the important roles to the development of LVH and the expression of P53, Bax, Bcl -2 protein. Valsartan can inhibit the development of LVH and contribute to systolic dysfunction of Goldblatt Rat. Spironolactone can partly inhibit the development of LVH and contribute to systolic dysfunction of Goldblatt Rat.