科研之友
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摘要
BACKGROUND AND PURPOSE Nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener and nitric oxide donor, is used in the treatment of angina and acute heart failure. Here we investigated the effects of two K(ATP) channel openers, nicorandil and cromakalim on ischaemia reperfusion (I-R) injury in the kidney. EXPERIMENTAL APPROACH Right nephrectomy was performed in 8-week-old male Sprague-Dawley rats and they were then divided into six groups: control group; I-R, including 30 min of left renal ischaemia followed by 24 h of reperfusion; I-R groups plus nicorandil 3 or 10 mg center dot kg-1 i.p.; and I-R groups plus cromakalim 100 or 300 mu g center dot kg-1 i.p. After reperfusion, renal function was estimated by serum creatinine (SCr), urinary albumin : creatinine ratio (ACR) and urinary beta 2-microglobulin (beta 2-MG). Levels of K(ATP) channel subtypes were investigated by Western blot. Kidney sections were stained for 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine. KEY RESULTS Renal I-R induced significant increases in SCr, ACR and beta 2-MG levels compared with the control animals. Treatment with K(ATP) channel openers reduced urinary beta 2-MG levels, raised by I-R. Both K(IR)6.1 and K(IR)6.2 channels were expressed. Expression of K(IR)6.2 channels in the I-R group was lower than in the control group, which was restored to normal by treatment with K(ATP) channel openers. Histologically, severe acute tubular damage was observed in the I-R kidney and this damage was ameliorated by K(ATP) channel openers, dose-dependently. CONCLUSIONS AND IMPLICATIONS ATP-sensitive potassium channel openers protected against proximal tubule damage after I-R injury. Nicorandil could represent a powerful additional component in the treatment of patients undergoing partial nephrectomy or renal transplantation.
- 出版日期2011-5
