内皮素-1在醛固酮增多症大鼠模型肾脏纤维化过程中的作用及其意义  

The Role and Significance of Endothelin-l in the Development of Renal Fibrosis in Aldosterone-Infused Rats

作　　者：龚道静[1] 欧阳金枝[2] 王超[1] 倪栋[1] 闫永吉[1] 吴准[1] 李俊[1] 张旭[1,3] 

机构地区：[1]华中科技大学同济医学院附属同济医院泌尿外科,武汉430030 [2]解放军总医院内分泌科 [3]解放军总医院泌尿外科

出　　处：《临床泌尿外科杂志》2009年第10期779-782,787,共5页Journal of Clinical Urology

基　　金：国家杰出青年科学基金资助(编号30725040)

摘　　要：目的:观察内皮素-1(endothelin-1,ET-1)在醛固酮增多症大鼠肾脏中的表达情况,初步探讨临床上原发性醛固酮增多症术后持续性高血压的机制。方法:将SD大鼠随机分成三组,每组8只。采用经微量渗透泵持续释放给药的方式建立醛固酮大鼠模型。其中醛固酮组持续泵入醛固酮(1μg/h);醛固酮+螺内酯组除泵入等量醛固酮外,每日行螺内酯灌胃(100 mg·kg^(-1)·d^(-1));对照组仅泵空白溶剂。尾套法监测大鼠血压。4周后处死所有大鼠,测定血钾、钠、醛固酮浓度及血浆肾素活性。分别采用HE及Masson染色观察肾组织形态学改变及纤维化情况,采用RT-PCR及免疫组织化学方法检测肾皮质ET-1的表达及定位。结果:成功建立醛固酮增多症大鼠模型,醛固酮组血压2周后明显升高,血钾下降,呈现低肾素、高醛固酮特征,与对照组相比差异具有统计学意义(P<0.01)。醛固酮组肾组织形态学观察可见明显纤维化,ET-1表达明显高于对照组(P<0.01)。螺内酯可抑制醛固酮的上述效应(P<0.01)。结论:醛固酮可能通过上调ET-1的表达,促进肾脏纤维化,造成肾脏不可逆性损害,其可能是临床上原发性醛固酮增多症术后持续性高血压的机制之一。Objective： To observe the expression of endothelin 1 （ET 1） in the kidney of aldosterone-infused rats, and then to explore initially the mechanism of persistense of hypertension of the patients of primary hyperaldosteronism after operation. Methods：SD rats were randomly divided into 3 groups, with each group 8 rats. Aldosterone group： aldosterone infusion（1 μg/h） via a mini-osmotic pump implanted subcutaneously; Aldosterone plus spironolactone group： aldosterone infusion and gastric gavage with spironolactone（100 mg·kg^-1· d^-1）;Control group： only vehicle infusion. Systolic blood pressure（SBP） was monitored by the tail-cuff method. All of the rats were put to death after 4 weeks and the concentration of potassium, sodium, and aldosterone in blood serum and plasma renin activity （PRA） were measured. Observing the change of histomorphology and fibrosis in kidney via HE and Masson dying, respectively. RT- PCR and immunohistoehemistry for detecting the expression and localization of ET-1 in renal tissue, respectively. Results： Rat models of hyperaldosteronism were established successful ly, aldosterone significantly increased SBP after 2 weeks and decreased the concentration of potassium, presenting the characteristic of low renin and high-aldosterone compared to control group （P〈0.01）. Aldosterone promoted renal fibrosis and significantly up-regulated the expression of ET-1 compared to control group（P〈0.01）, spirono lactone could inhibite the effect above（P〈0.01）. Conclusions： Aldosterone may promote renal fibrosis via up-regu luting the expression of ET-1, and lead to irreversible renal leisions subsequently, which may be one of the mecha nisms of persistence of hypertension of patients of primary hyperaldosteronism after operation.

关 键 词：内皮素 醛固酮 肾脏 纤维化 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]