Yang Lichuan, Fan Junming, Mi Xuhua, Liu Xianrong, Xu Guozhang
Department of Nephrology, West China Hospital, Sichuan Univerdity, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2003 Apr;34(2):317-9.
To investigate the possible mechanism of angiotensin II receptor blockage (Losartan) for the decreasing of proteinuria and the protection of renal function in diabetic rats.
Sixty Wistar rats were divided into 3 groups: Losartan treatment group, diabetes mellitus (DM) model group, and control group. All were treated accordingly for 4 weeks. 24 hours urine protein count, creatinin clearance rate (Ccr), mean arterial pressure (MAP), kidney weight/body weight, ET-1 in blood and urine, IV collagen and fibronectin (FN) in kidney tissue were determined at 1, 2, 4 weeks.
In DM model group, the 24 hours urine protein count and MAP, compared with control, increased significantly (P < 0.05) and reached peak at 2 weeks; the decrease of Ccr and the increase of kidney weight/body weight were observed; meanwhile, by immunohistochemistry, increased expression levels of FN, IV collagen were shown in kidney tissues, especially on basement membrane, and significant increase of ET-1 level in blood and urine was also noted. In Losartan treatment group, all of MPA, 24 hours urine protein count, kidney weight/body weight and Ccr decreased, compared with those of model group; ET-1 in blood and urine decreased too, especially the decreasing of ET-1 in urine (P < 0.01). And the expression level of FN and IV collagen was just as small as that in control group.
Losartan may play a role in inhibiting the synthesis and secretion of ET-1 in kidney and thus it will contribute to the decreasing of proteinuria and the protection of renal function.
探讨血管紧张素Ⅱ受体阻滞剂(氯沙坦)降低糖尿病大鼠蛋白尿及保护肾功能的可能机制。
将60只Wistar大鼠分为3组:氯沙坦治疗组、糖尿病(DM)模型组和对照组。均相应治疗4周。于第1、2、4周测定24小时尿蛋白定量、肌酐清除率(Ccr)、平均动脉压(MAP)、肾重/体重、血及尿中ET-1、肾组织Ⅳ型胶原和纤维连接蛋白(FN)。
DM模型组24小时尿蛋白定量和MAP较对照组显著升高(P<0.05),并于2周达峰值;Ccr降低,肾重/体重增加;同时,免疫组化显示肾组织中FN、Ⅳ型胶原表达水平升高,尤其在基底膜,血及尿中ET-1水平也显著升高。氯沙坦治疗组与模型组比较,MAP、24小时尿蛋白定量、肾重/体重和Ccr均降低;血及尿中ET-1也降低,尤其是尿中ET-1降低(P<0.01)。且FN和Ⅳ型胶原表达水平与对照组相近。
氯沙坦可能通过抑制肾脏ET-1的合成与分泌发挥作用,从而有助于降低蛋白尿和保护肾功能。