醛固酮诱导大鼠肾脏衰老机制研究

Mechanism of aldosterone induced rat kdney senescence

目的观察醛固酮是否诱导肾脏衰老。方法将大鼠右肾切除后随机分为4组:对照组(n=10)、模型组(n=8)、依普利酮组(100 mg.kg-1.d-1;n=8)及肼苯哒嗪组(80 mg.L-1,饮用;n=10);除对照组外,其余各组分别泵入醛固酮(0.75μg.h-1),观察5周后肾脏衰老改变。结果醛固酮可诱导5周龄的大鼠肾组织衰老标记物β-gal、p53和p21表达升高,SIRT1基因表达下降,伴高血压及蛋白尿、N-乙酰基-β-D氨基葡萄糖苷酶(NAG)的排泄率增加,这些变化可以被依普利酮阻断,但是肼苯哒嗪影响不大。结论醛固酮诱导肾小管上皮细胞损伤和衰老是通过醛固酮受体和p21依赖的途径。

Objective To investigate whether aldosterone induces cell senescence in the kidney. Methods Rats were randomly separated to vehicle （n = 10） ; aldosterone （0. 75 ug. h-1; n =8） ; aldosterone ＋ eplerenone （100 mg . kg-1. d-1 ; n = 8） ; aldosterone ＋ hydralazine （80 mg . L-1 in drinking water; n = 10）. Results Aldosterone induced rats for 5 weeks exhibited by increased expression of senescence - associated β - galactosidase, p53 and cyclin - dependent kinase inhibitor （ p21 ） , and decreased expression of SIRT1. While, rats also showed hypertension and increased urinary excretion rates of proteins and N - acetyl -β- D- glucosaminidase by aldosterone infusion. These changes were abolished by eplerenone, a mineralocorticoid receptor （MR） antagonist, but unaffected by hydralazine （80 mg/liter in drinking water）. Conclusion These findings indicate that aldosterone induces renal senescence in proximal tubular cells via the MR and p21 -dependent pathway, which may be involved in aldosterone-induced renal injury.