Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-I overproduction
Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-I overproduction
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DOI：
10.1042/cs103s434s
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发表时间：
2002-08-01
期刊：
影响因子：
6
通讯作者：
Matsumura, Y
中科院分区：
文献类型：
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作者：
Takaoka, M;Yuba, M;Matsumura, Y
我们研究了 17β-雌二醇治疗是否对患有缺血性急性肾衰竭 (ARF) 的雄性大鼠具有肾脏保护作用。我们还检查了 17β-雌二醇的作用是否伴随着抑制缺血后肾脏中内皮素-1 生成的增强。对侧肾切除术后 2 周，夹闭左肾动脉和静脉 45 分钟，然后再灌注，诱导缺血性 ARF。测量肾功能参数，如血尿素氮、血浆肌酐和肌酐清除率，以测试类固醇激素的有效性。 ARF大鼠的肾功能在再灌注24小时后显着下降。通过用17β-雌二醇（20或100μg/kg，静脉注射）预处理，缺血/再灌注引起的肾功能障碍得到剂量依赖性改善。对未经治疗的 ARF 大鼠的肾脏进行组织病理学检查，发现严重病变，如肾小管坏死、肾小管内蛋白管型和髓质充血，所有这些都在较高剂量的 17β-雌二醇后得到显着改善。此外，缺血/再灌注后肾脏中的内皮素-1 含量显着增加约 10%。是假手术大鼠的 2 倍，并且这种升高被 17β-雌二醇治疗剂量依赖性地抑制。这些结果表明，雌激素对缺血/再灌注引起的肾功能障碍和组织损伤具有保护作用，可能是通过抑制缺血后肾脏中内皮素-1 的过量产生来实现的。
We investigated whether the treatment with 17beta-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17beta-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24 h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17beta-oestradiol (20 or 100 mug/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17beta-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17beta-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.