Protective effect of sirolimus on water-electrolyte imbalance following bilateral ureteral obstruction in rats / 中华泌尿外科杂志

ABSTRACT

Objective To explore the molecular mechanism of renal function defects after urinary obstruction and investigate the effect of sirolimus on the expression of γ-ENaC,Na + K + ATPase and AQP2,and its mechanism of renal Water-Electrolyte imbalance following bilateral ureteral obstruction (BUO) in rat kidneys.Methods Forty-eight rats were randomly divided into a sham operation group ( sham group),a BUO group,and a sirolimus treatment after BUO group.Bilateral ureters were exposed and occluded with ligature in the BUO and sirolimus treatment groups.Twenty-four hours later,the obstructed ureters were decompressed by removal of the ligature.The sham animal group underwent identical surgical procedures,but the ureter was simply dissected without removal of the ligature.The sirolimus treatment groups was given sirolimus intragastricly 0.4 ml per day (2 mg/kg · d) from the day before surgery until the rats were scari fled.The sham and BUO groups were given the same volume of intragastric saline.The urine and blood were collected at 4 d,7 d after surgery,and the functional data were observed.The expression of γ-ENaC,Na+K + ATPase and AQP2 were examined by immnohistochemistry and immunoblotting.Results On day four and seven post ureteral obstruction release,urine volume in the BUO group were (85.31 ± 13.15,66.39 ±10.56 ml),significantly higher than that of sham operation (35.36 ± 7.74,33.90 ± 8.03 ml) and sirolimus treatment groups (69.81 ± 10.70 ml,48.57 ± 9.01 ml) (P ＜ 0.05 ).Urine sodium concentrations in the BUO group were (42.17 ± 7.35 mmol/L,43.63 ± 18.39 mmoL/L),significantly lower than that of sham operation ( 170.56 ± 18.39 mmoL/L,172.52 ± 7.35 mmol/L) and sirolimus treatment groups (76.18 ± 13.20 mmol/L,134.28 ± 13.20 mmol/L),P ＜ 0.05.Immunoblotting assay showed that,on day four and seven post rats ureteral obstructions were released,integral optical density of γ-ENaC (2.09 ±0.32,2.27 ±0.35),Na+ K+ATP enzyme (2.41 ±0.48,2.67 ±0.43) and AQP2 (2.17 ±0.45,2.63 ±0.28) in the sirolimus treatment group were significantly higher than those of BUO group ( 1.28 ± 0.21,1.45 ±0.17) (1.99 ±0.28,2.18±0.24) (0.93 ±0.22,1.31 ±0.16),but still lower than the sham group (2.58±0.51,2.60±0.56) (2.89±0.53,2.97 ±0.66) (3.05 ±0.63,3.10±0.67).There were significant differences among all the three groups ( P ＜ 0.05 ).Conclusions The downregulation of γ-ENaC,Na + K + ATPase and AQP2 expression after BUO may contribute to the impaired renal tubular sodium reabsorption,decreased urinary concentration,and postobstructive polyuria.Sirolimus treatment significantly prevents impairment in renal function and also prevents downregulation of y-ENaC,Na + K+ ATPase and AQP2during BUO,demonstrating a marked renoprotective effect of sirolimus treatment in conditions with urinary tract obstruction.