阿利吉仑对阿霉素肾病小鼠肾脏的保护作用

摘要

目的：探讨阿利吉仑对阿霉素肾病小鼠肾脏的保护作用。方法通过尾静脉注射阿霉素建立阿霉素肾病模型小鼠24只，随机分为阿霉素肾病组、阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组各6只，另取同龄BALB/c小鼠6只作为正常对照组。比较各组阿霉素注射后第2、6周24 h尿蛋白定量及肾功能的差异；处死小鼠后，取各组肾组织石蜡包埋，切片行PAS、HE和Masson染色，观察肾小球硬化程度和肾小管损害程度。结果阿霉素肾病小鼠表现为蛋白尿、低蛋白血症并伴有进行性肾功能下降，出现肾小球硬化及小管间质损害。与阿霉素肾病组比较，阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组24 h尿蛋白均有显著改善，血清白蛋白明显上升（P均＜0．05）。与阿霉素肾病组比较，阿利吉仑组、缬沙坦组及阿利吉仑＋缬沙坦组均可明显减轻肾小球硬化和肾小管间质损害（P均＜0．05），但阿利吉仑＋缬沙坦组可明显改善肾间质纤维化（P均＜0．05）。结论阿利吉仑对阿霉素肾病小鼠具有肾脏保护作用，与缬沙坦联合应用可明显改善肾间质纤维化程度。%Objective To investigate the protective effect of aliskiren on kidney of mice with adriamycin nephropathy. Methods Twenty-four male BALB/c mice were subjected to the single tail vein injection of adriamycin to establish adriamycin nephropathy models.Then they were randomly divided into 4 groups, 6 in each group: the adriamycin nephropathy group, aliskiren group, valsartan group, and aliskiren +valsartan group;another 6 male BALB/c mice with the same age were selected as the control group.At week 2 and 6 after being injected adriamycin, the differences in urinary protein and kidney function were compared in each group.Mice were sacrificed at week 6.The paraffin-embedded sections of the kidney were stained by PAS, Masson and HE staining.The degrees of glomerular sclerosis and renal tubular damage were observed .Results Mice in the ad-riamycin nephropathy group showed proteinuria, hypoalbuminemia combined with progressive renal function decline, and ap-peared glomerulosclerosis and tubulointerstitial injury.Compared with the adriamycin nephropathy group, proteinuria improved and serum albumin increased significantly in the aliskiren group, valsartan group and aliskiren +valsartan group ( all P<0.05).Histological evaluation revealed that aliskiren group, valsartan group and aliskiren +valsartan group could significantly reduce the glomerulosclerosis and tubulointerstitial lesions (all P<0.05), but the aliskiren +valsartan group significantly im-proved the renal interstitial fibrosis (all P<0.05).Conclusion Aliskiren has protective effect on kidney in mice with adriamy-cin induced nephropathy and its combined application of valsartan can significantly improve the interstitial fibrosis .