波生坦与雷米普利对单侧输尿管梗阻大鼠的肾脏保护作用对比研究  

A Compare Study Between Bosentan and Ramipril in Rats with Unilateral Ureteral Obstruction

作　　者：邢国兰[1] 刘章锁[1] 文建国 王立东[3] 

机构地区：[1]郑州大学第一附属医院肾内科,河南郑州450052 [2]河南省高等学校临床医学重点学科开放实验 [3]郑州大学基础医学院

出　　处：《中国误诊学杂志》2005年第13期2403-2405,共3页Chinese Journal of Misdiagnostics

基　　金：河南省杰出人才创新基金资助项目(编号:0221002000);河南省杰出青年科学基金资助项目(编号:02120001100)

摘　　要：目的:应用雷米普利(Ramipril)与波生坦(Bosentan)对单侧输尿管梗阻(uuo)大鼠模型进行干预,比较两药物对肾脏病理改变的影响,并探讨其机制。方法:雄性Wistar大鼠,随机分为假手术组(S)、手术组(uuo)、波生坦组(Bos)和雷米普利组(Ram)。制备uuo大鼠模型、Bos组给予波生坦灌胃、Ram组给予雷米普利灌胃,术后4个时间点观察血常规、肾脏大体和组织病理、免疫组化测定肾组织转化生长因子β-1(TGFβ-1)表达,放射免疫法测定血、梗阻侧肾脏残尿ET-1浓度。结果:uuo组梗阻侧肾脏大体观:体积增大、肾盂扩张、肾皮质变薄、组织病理改变,显示间质纤维化。TGFβ-1阳性细胞数表达增多。Bos组和Ram组肾脏大体观、组织病理改变、TGFβ-1阳性细胞数表达较uuo组明显减轻,Bos组和Ram组之间比较无显著差异。梗阻侧肾脏残尿ET-1浓度和uuo组、Bos组、Ram组与S组比较明显升高,uuo组、Bos组、Ram组之间比较无显著差异。结论:雷米普利与波生坦对uuo大鼠肾间质纤维化干预效果相似,其机制可能通过拮抗内皮素受体和下调转化生长因子β-1起作用。Objective：To compare different effects of ramipril and bosentan in rats with unilateral ureteral obstruction （UUO）. Methods：Wistar Rats were evenly divided into four groups. UUO group were subjected to complete ligation of left ureter. S group with sham operation were used as control. Bos group were subjected to complete ligation of left ureter and to perfuse stomach with bosentan suspension. Ram group were subjected to complete ligation of left ureter and to perfuse stomach with ramipril suspension. 3 mice per group killed at 5,10,15,20 d. We examined renal pathological change and the TGFβ-1 expressions in kidney of all these rats using immunohistochemistry analisis method. The plasma and ureteral obstructive kidney urinary concentration of ET-1 was determined by radioimmunoassay. Resuits：In Bos and UUO groups,the urinary concentration of ET-1 increased substantially and the expression of TGFβ-1 were much higher than those in the S group. At the same time,tubulointerstitial fibrosis was present in the kidney of rats in Bos .UUO and Ram group. But the expression of TGFβ-1 and tubulointerstitial fibrosis in Bos group were lower than UUO group. There was no significant difference of intervention effects between bosentan and ramipril conclusion in the study. Conclusion ：Pharmacologycal effects of Bosentan and ramipril on unilateral ureteral obstruction rats are quite similar. These effects may result from the down-regulation of TGFβ-1 and antergia ET machanism in kidney tissue.

关 键 词：输尿管梗阻/药物疗法 肾/药物作用 雷米普利/治疗应用 磺胺类/治疗应用 受体/拮抗剂和抑制剂 

分 类 号：R693.2[医药卫生—泌尿科学]