速尿对整体大鼠肾11β-羟基类固醇脱氢酶活性的影响

The effects of furosemide on renal 11β-hydroxysteroid dehydrogenase and serum electrolytes in intact rats

目的 研究速尿对整体大鼠肾 11β -羟基类固醇脱氢酶活性的影响 ,探讨速尿引起低血钾可能的新生化机制。方法 大鼠给予速尿单次和多次 (bid× 2 0d)灌胃 ,HPLC法测定大鼠尿中脱氢皮质酮 (A)与皮质酮 (B)的比值。全自动生化分析仪测定给药后血K+ 、Na+ 、Cl-浓度。结果 速尿 (40、10 0、2 5 0mg·kg-1)单次和 (10、2 0、10 0mg·kg-1)多次给药后 ,尿中A/B比值分别下降了 2 9.0 %、5 8.6 %、6 0 .9%和 14 .4 %、36 .0 %、4 4 .9%。速尿 (2 0、10 0mg·kg-1)连续给药 2 0d ,血钾较对照组显著降低 (P <0 .0 1) ,血钾降低与A/B的降低呈正相关 (P <0 .0 1)。结论 速尿在体给药可抑制肾 11β-HSD活性。

Objective To investigate the effects of furosemide (Fur) on 11β-hydroxysteroid dehydrogenase (11β-HSD) activity and serum electrolytes in intact rats, and the correlation between the decrease of 11β-HSD activity and the hypokalemia induced by Fur. Methods SD rats were given Fur of single dose (40, 100, and 250 mg·kg -1 ) or of successive doses (10, 20, and 100 mg·kg -1 , bid×20 d) by gavage. The activity of 11β-HSD was evaluated by measuring the ratio of dehydrocorticosterone (A) to corticosterone (B) in urine by HPLC method. Results After giving single-dose Fur and multiple-dose Fur, the urinary ratio of A/B was reduced by 29.0 %, 58.6 %, 60.9 % and 14.4 %, 36.0 %, 44.9 % respectively. The serum potassium was significantly reduced by multiple-dose Fur (20 and 100 mg·kg -1 ) (P<0.01). The reduction of serum potassium was positively correlated with the lowering of A/B ratio (P<0.01). Conclusion The inhibition of renal 11β-HSD activity may be a new biochemical mechanism for hypokalemia induced by Fur.