速尿对大鼠肾11β-羟基类固醇脱氢酶活性的抑制作用与其低血钾的相关性

摘要

目的：研究速尿对大鼠11β-羟基类固醇脱氢酶活性rn的抑制作用与低血钾的相关性.方法：SD大鼠给rn予速尿40，100和250 mg/kg单次灌胃，或10，20和rn100 mg/kg连续灌胃20 d，每天两次.HPLC法测定rn尿中脱氢皮质酮(A)与皮质酮(B)的比率及肾皮质微rn粒体酶对皮质酮的转化率评定肾11β-羟基类固醇脱rn氢酶活性.结果：速尿(40，100，250 mg/kg)单次或rn(10，20，100 mg/kg)连续灌胃，大鼠尿中A/B分别rn降低了29.0％，58.6％，60.9％(0-2 h)和rn14.4％，36.0％，44.9％.皮质酮的转化率降低了rn29％，33％，37％和6％，17％，23％，速尿(20，rn100 mg/kg)连续给药组血钾显著降低(P＜0.01).rn血钾的降低与皮质酮的转化率及尿中A/B值的变化rn成正相关.结论：速尿对11β-羟基类固醇脱氢酶活rn性的抑制可能是其引起低血钾的另一个重要的基本rn生化机制.%AIM: To investigate the correlation between decrease of rn11β-hydroxysteroid dehydrogenase (11β-HSD) activity rnand hypokalemia induced by furosemide (Fur) in rats.rnMETHODS: SD rats were given single dose or rnsuccessive doses of Fur by gavage. The activity of 11β-rnHSD was evaluated by measuring the ratio of 11-dehydro rncorticosterone (A) and corticosterone (B) in urine and rnconversion rate of B to A in renal cortex microsome rnpreparation was determined with HPLC. RESULTS:rnAfter giving single dose of Fur (40, 100, and 250 mg/rnkg) or multiple doses of Fur (10, 20, and 100 mg/kg,rnbid × 20 d), the ratio of A/B was reduced by 29.0 %,rn58.6%, and 60.9 % at0-2 h; 14.4 %, 36.0 %,rnand 44.9 %, respectively; the conversion rate of B to A rnwas decreased by 29 %, 33 %, and 37 %; 6 %,rn17 %, and 23 %, respectively. The serum potassium rnwas significantly reduced by multiple doses of Fur (20rnand 100 mg/kg , bid × 20 d) (P ＜ 0.01). The rnreduction in serum potassium was positively correlated rnwith the lowering of A/B ratio and the conversion of B to rnA (P ＜ 0.01 ). CONCLUSION: The inhibition of rnrenal 11β-HSD activity may be another new biochemical rnmechanism for hypokalemia induced by Fur.