Aortic Cell Apoptosis in Rat Primary Aldosteronism Model
Aortic Cell Apoptosis in Rat Primary Aldosteronism Model
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DOI：
10.1007/s11596-010-0362-3
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发表时间：
2010-06-01
影响因子：
--
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
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作者：
Yan, Yongji;Ouyang, Jinzhi;Zhang, Xu
本研究旨在探讨醛固酮在体内是否能诱导血管细胞凋亡。32只雄性大鼠随机分为4组：溶剂组（对照组）、醛固酮组、醛固酮加依普利酮组或肼屈嗪组。然后，他们被植入一个渗透性微型泵，注入醛固酮或车辆。采用尾袖法每周测量一次收缩压（SBP）。8周后用放射免疫法测定血浆醛固酮浓度（PAC）和肾素活性（PRA）。TUNEL法检测主动脉细胞凋亡。Western blotting检测细胞色素c和caspase-3的表达，免疫组化和Western blotting检测Bax和Bcl-2的表达。结果显示，与对照组相比，醛固酮组大鼠收缩压（SBP）升高; PAC显著升高，PRA显著降低;主动脉血管细胞凋亡增加，细胞色素c和caspase-3活性升高; Bax蛋白表达显著上调，Bcl-2表达显著下调。醛固酮的这些作用在与依普利酮共同给药后被显著抑制，但与肼苯哒嗪不一起。研究结果表明，醛固酮通过盐皮质激素受体直接作用于主动脉，诱导血管细胞凋亡，与血压无关，这可能是醛固酮介导的血管损伤的重要机制之一。
This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo. Thirty-two male rats were randomly divided into 4 groups: vehicle (control), aldosterone, aldosterone plus eplerenone or hydralazine. They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method. After 8 weeks, plasma aldosterone concentration (PAC) and renin activity (PRA) were determined by radioimmunoassay. Aortic apoptosis was examined by TUNEL assay. The levels of cytochrome c and caspase-3 were determined by Western blotting and the expression of Bax and Bcl-2 was detected by immnuohistochemistry and Western blotting. The results showed that as compared with control group, aldosterone-infused rats exhibited: (1) an increase in SBP; (2) significantly elevated PAC with depressed PRA; (3) elevated aortic vascular cell apoptosis accompanied with higher levels of cytochrome c and activated caspase-3; and (4) significantly up-regulated Bax protein with down-regulated Bcl-2. These effects of aldosterone were significantly inhibited after co-administration with eplerenone but not with hydralazine. It was concluded that aldosterone induced vascular cell apoptosis by its direct effect on the aorta via mineralocorticoid receptors and independently of blood pressure, which may contribute to aldosterone-mediated vascular injury.