醛固酮腺瘤模型大鼠主动脉平滑肌细胞增殖与mdm2和p53的表达

目的 初步探讨肾上腺醛固酮腺瘤血管重构的机制.方法 将微量渗透泵植入大鼠皮下,随机分为对照组、腺瘤组、腺瘤+依普利酮组和腺瘤+肼苯哒嗪组.8周后检测主动脉平滑肌细胞的增殖状态和mdm2、p53的表达.结果 ①成功建立大鼠醛固酮腺瘤模型;②与对照组相比,腺瘤组大鼠主动脉平滑肌细胞增生活跃(P＜0.05);MDM2 mRNA和蛋白表达上调(P＜0.05);而p53只在蛋白水平增加(P＜0.05);③相较于肼苯哒嗪,依普利酮能抑制醛固酮的作用(P＜0.05).结论 醛固酮通过诱导mdm2表达而逆转p53的细胞周期阻滞作用,促使平滑肌细胞增殖,可能是醛固酮腺瘤血管重构的原因之一.

Expressions of MDM2 and p53 and Proliferation of Aorta of Rat Models of Aldosterone-Producing Adenoma

Objective To preliminarily study the mechanism of vascular remodeling resulting from aldosterone-producing adenoma(APA).Methods 32 Sprague-Dawley rats,each subcutaneously implanted with an osmotic mini-pump,were randomly divided into 4 groups:vehicle as control;aldosterone(1 μg/h);aldosterone plus eplerenone(100 mg/kg/day)and aldosterone plus hydralazine(25 mg/kg/day).After 8 weeks,the proliferation of aortic smooth muscle cells(ASMCs)and the expressions of MDM2 and p53 genes were examined.Results ① The rat APA models were successfully established;② Compared with controls,APA rats showed more proliferating cells with the proliferative marker proliferating cell nuclear antigen(PCNA),up-regulated expressions of MDM2 at mRNA and protein level in the aorta,and elevated p53 at protein level(P＜0.05).③ These All aldosterone induced effects above were inhibited by eplerenone but not by hydralazine.Conclusion Aldosterone promotes ASMC proliferation,which contributes to aldosterone-induced vascular remodeling,at least partially by upregulating the expression of MDM2 that is able to inhibit the effect of cell cycle arrest by simultaneously elevated p53.