缬沙坦和雷米普利对5/6肾切除大鼠肾间质微血管的作用  

Effects of valsartan and ramipril on the peri-tubular microangium in rats with 5/6 subtotal nephrectomy

作　　者：章斌[1] 王伟铭[1] 史浩[1] 赵青[1] 陈楠[1] 

机构地区：[1]上海第二医科大学附属瑞金医院肾脏科,上海200025

出　　处：《肾脏病与透析肾移植杂志》2003年第1期28-31,40,共5页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：上海市卫生局医学领先专业学科基金 (NO :983 0 0 9)

摘　　要：目的 :观察大鼠 5 /6肾切除模型中间质微血管病变的特点及药物缬沙坦和雷米普利对其的干预作用。　 方法 :以SD大鼠 5 /6肾切除建立肾间质纤维化 (RIF)动物模型 ,设正常组 (n =6 ) ,假手术组 (n =6 ) ,手术组(n =7) ,氨氯地平组 (n =6 ) ,缬沙坦组 (n =10 ) ,雷米普利组 (n =10 )。术后定时测定 2 4h尿蛋白排泄量及血压。 12周后取材 ,留取血样 ,2 4h尿样及肾组织。常规病理检查判断RIF及肾小管间质损伤程度 ;应用免疫组化方法显示肾脏毛细血管。　 结果 :与正常组和假手术组相比 ,手术组RIF明显 ,间质微血管病变严重 ,肾小管周围毛细血管(PTC)密度明显减少 (36 3 2 9± 70 .99vs 798.17± 6 6 .5 3,776 .10± 5 1.2 9,P <0 0 1)。而缬沙坦和雷米普利能延缓RIF及间质微血管病变 ,并改善肾功能 ,与手术组相比 ,两组PTC密度均明显改善 (45 5 5 0± 6 2 .98,P <0 .0 5和 4 6 5 6 0±5 7 38,P <0 0 1)。而氨氯地平血压控制组与手术组PTC密度无差异。　 结论 :间质微血管病变不仅是RIF的特征性病理改变 ,而且在RIF及肾功能减退中可能起重要作用。缬沙坦和雷米普利延缓RIF和对肾功能的保护作用与间质微血管病变的改善有关 ,其机制可能与血管紧张素Ⅱ相关联。Objective:To investigate the effects of valsartan and ramipril on the peri-tubular microangium in rats with 5/6 subtotal nephrectomy (STNx). Th renal subtotal ablation model was established by surgically 5/6 renal resection of the male Sprague-Dawley(SD) rats.Six groups were divided in our experimental protocol.They were Normal ( n =6),Sham ( n =6),STNx( n =7),STNx treated with amlodipine (STNxA, n =6),STNx treated with valsartan (STNxV, n =10),and STNx treated with ramipril (STNxR, n =10).The urinary protein excretion rates per day and systolic arterial pressure were measured periodically.The all of rats were sacrificed at the end of 12 th week after operation.Tubulointerstitial injury,interstitial fibrosis and renal capillary were scored semi-quantitively by morphological and immunohistochemical analysis. It was found that there was significant tubulointerstitial injury and interstitial fibrosis,with more markedly decreased prei-tubular capillary density,in the STNx group compared with that in Normal and Sham group (363±70 9) vs 798±66.5,776±51.3/mm 2, P <0.01).Tubulointerstitial injury,interstitial fibrosis,peri-tubular capillary loss and impaired renal function were ameliorated by the administration of valsartan and ramipril compared with that in STNx group (455±62.9/mm 2, P <0.05 and 466±57.4/mm 2, P <0.01).As regard to peri-tubular capillary density,there were no marked differences between STNxA group and STNx group. The change of prei-tubular microcirculation,one of pathological alterations characterized in renal interstitial fibrosis,is involved in pathogenesis of progressive interstitial fibrosis and impairment of renal function.The favorable blood pressure-dependent effects of valsartan and ramipril on the peri-tubular microcirculation may contribute to amelioration of interstitial fibrosis,which could be related to Angiotensin Ⅱ.

关 键 词：肾切除 肾间质微血管病变 缬沙坦 雷米普利 血管紧张素Ⅱ 

分 类 号：R965[医药卫生—药理学]