Department of Nephrology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, PR China.
Ren Fail. 2011;33(2):225-32. doi: 10.3109/0886022X.2010.541586.
To investigate the renal microvascular injury in acute aristolochic acid nephropathy (AAN) and the protective effects of prostaglandin E1 (PGE1) in acute AAN.
Female Sprague-Dawley rats were randomly divided into three groups. The rats in PGE1 group received Caulis Aristolochia manshuriensis (CAM) decoction by gavage for 5 days, and PGE1 was given by vena caudalis before gavage. The rats in model group were gavaged with CAM for 5 days, and the same dose of 0.9% physiologic saline was given by vena caudalis. The rats in control group only received an equal daily volume of saline solution by gavage. Animals were killed at days 3, 5, and 7. Blood urea nitrogen (BUN), serum creatinine, and urinary protein were monitored before killing. Microvascular density was determined by JG12 immunostaining. The expression of angiogenic factor was assessed by vascular endothelial growth factor (VEGF). Tubulointerstitial hypoxia was assessed by hypoxia-inducible factor-1α (HIF-1α) expression.
CAM induced a significant decrease in VEGF expression and microvascular density in the kidney tissue, accompanied by a significant increase in HIF-1α, which reduced renal function and increased 24-h urinary protein excretion rates. PGE1 lessened the capillary loss, relieved hypoxia, and protected renal function. No significant pathological changes were found in control rats.
The renal microvascular injury in acute AAN is severe. PGE1 can significantly ameliorate the renal microvascular injury, relieve hypoxia, and protect renal function.
研究急性马兜铃酸肾病(AAN)中的肾微血管损伤以及前列腺素 E1(PGE1)在急性 AAN 中的保护作用。
将雌性 Sprague-Dawley 大鼠随机分为 3 组。PGE1 组大鼠通过灌胃给予马兜铃酸(CAM)煎剂 5 天,在灌胃前通过尾静脉给予 PGE1。模型组大鼠通过灌胃给予 CAM 5 天,尾静脉给予相同剂量的 0.9%生理盐水。对照组大鼠仅通过灌胃给予等量的生理盐水。处死前监测血尿素氮(BUN)、血清肌酐和尿蛋白。通过 JG12 免疫染色测定微血管密度。通过血管内皮生长因子(VEGF)评估血管生成因子的表达。通过缺氧诱导因子-1α(HIF-1α)的表达评估肾小管间质缺氧。
CAM 诱导肾脏组织中 VEGF 表达和微血管密度显著降低,同时 HIF-1α 显著增加,导致肾功能下降,24 小时尿蛋白排泄率增加。PGE1 减轻了毛细血管丢失,缓解了缺氧,保护了肾功能。对照组大鼠无明显病理变化。
急性 AAN 中的肾微血管损伤严重。PGE1 可显著改善急性 AAN 中的肾微血管损伤,缓解缺氧,保护肾功能。