厄贝沙坦对单侧输尿管梗阻大鼠肾间质纤维化干预作用

目的：观察血管紧张素Ⅱ受体拮抗剂厄贝沙坦对单侧输尿管梗阻大鼠肾组织结缔组织生长因子（CTGF）、骨形成蛋白-7（BMP-7）表达的影响,探讨厄贝沙坦保护肾脏的机制。方法：36只雄性Wistar大鼠随机分为厄贝沙坦治疗组、模型组、假手术组,每组12只。厄贝沙坦治疗组、模型组结扎大鼠左侧输尿管建立UUO模型,假手术组仅分离不结扎左侧输尿管,治疗组给予厄贝沙坦20mg/kg·d,假手术组、模型组每天给予相同剂量的生理盐水。每组分别于14d和28d各处死6只大鼠,并留取左侧肾脏组织做HE、MASSON染色,免疫组化法测定CTGF、BMP-7的表达。结果：与假手术组比较,厄贝沙坦治疗组、模型组的CTGF表达升高（P〈0.01）,而治疗组CTGF的表达低于模型组（P〈0.01）,治疗组肾间质纤维化程度也低于模型组（P〈0.01）。与假手术比较,治疗组、模型组BMP-7表达降低（P〈0.01）,且治疗组BMP-7表达高于模型组（P〈0.01）。结论：肾间质纤维化进展过程中厄贝沙坦治疗组CTGF表达逐渐减少,BMP-7表达逐渐增加。厄贝沙坦对肾脏的保护作用可能是通过减少CTGF的表达和增加BMP-7的表达。

The intervention effect of Irbesartan on renal Interstitial fibrosis in UUO rats

Objective： To investigate the effect of Irbesartan on the expression of connective tissue growth factor （CTGF）, bone morphogenetic protein- 7 （BMP- 7） in rats after unilateral ureteral obstruction ; and to discuss the mechanism that renoprotective effects of Irbesartan on kidney. Methods ： 36 WISTAR rats were ran- domly divided into sham-operation, model and Irbesartan groups with 12 rats in each group. Rats in model and Irbesartan group were obstructed left ureter. Rats in sham group were manipulated but not ligated. Rats in Irbesartan group received 20mg/kg. Irbesartan, and rats in model and sham operation group received equal vol- ume Saline each day. Six rats of each group were killed respectively at 14 and 28 days after the operations. We used HE and MAASSON stain to examine the area of pathological changes. Immunohistochemistry was used on renal tissue for the expression of connective tissue growth factor and bone morphogenetic protein-7. Results： Compared with the sham group, the expressions of CTGF in UUO and Irbesartan treatment group were higher （P ~ 0.01）, while the expression of CTGF in treatment group was lower than that in UUO group （P 〈 0.01）, and the renal interstitial fibrosis degree of the treatment group was lower than that in UUO group （P 〈 0. 05）, too. Compared with the sham group, the expression of BMP- 7 in UUO and treatment group was lower （P 〈 0. 01）, and the expression of BMP-7 in treatment group was higher than that in UUO group （P 〈 0.01）. Conclusion. With the obstruction time prolonged, the expression of CTGF decreased gradually in Irbesartan groups,and the expression of BMP-7 increased gradually. Irbesartan can protect renal function and delay the progression of renal interstitial fibrosis. Decreasing the expression of CTGF and increasing the expres- sion of BMP-7 are the probable mechanism.