Effect of local aldosterone on renal epithelial-mesenchymal transition in diabetic nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To explore the effect of aldosterone on renal epithelialmesenchymal transition in streptozocin(STZ)-induced diabetic nephropathy rats. Methods Wistar rats were intraperitoneally injected with STZ(60 mg/kg)for the preparation of diabetic model.After 4 weeks,the rats with urinary protein＞30 mg/d were regarded as successful diabetic nephropathy(n=16),and were randomly divided into diabetic nephropathy(DN group,n=8)and spironolactone group(SP group,n=8).Then eight healthy rats were selected randomly as control group(N group,n=8).SP group rats were treated with spironolactone 40 mg·kg-1·d-1,and N group and DN group rats were given equal water.After 8 weeks,rats were sacrificed to collect urine,blood plasma,kidney tissue for detection of 24 h urinary protein,creatinine and renal pathological changes.Aldosterone concentration in plasma and kidney tissue was detected by mdioimmunoassay;E-cadherin,α-SMA protein expression by immunohistochemistry,Western blotting; E-cadherin,α-SMA mRNA expression by RT-PCR. Results Compared with N group,serum creatinine, urinary protein excretion in the DN rats were significantly higher (P＜0.01,respectively), E-cadhefin protein and mRNA were significantly reduced (P＜0.01, respectively),α-SMA protein and mRNA expression was up-regulated (P＜0.01, respectively). Aldosterone level of kidney tissue in DN rats was increased obviously [(24.71±5.30) ng/g vs (16.38±2.85) ng/g, P＜0.01], which was positively correlated with urinary protein excretion, serum creatinine and α-SMA protein (r=0.737, 0.574, 0.688, P＜0.01, respectively), and negatively correlated with E-cadherin protein (r=-0.659, P＜0.O1). While no significant difference was found in serum aldosterone among three groups. Compared with DN rats, urinary protein excretion, serum creatinine were reduced (P＜0.01, respectively), E-cadherin protein and mRNA were increased (P＜0.01, respectively), α-SMA protein and mRNA expression were decreased (P ＜0.01, respectively) in SP group rats.Conclusions Local aldosterone involves in renal epithelial-mesenchymal transition in diabetic nephropathy rat. Spironolactone can block the effect of aldosterone and play a role in renal protection.