骨形态发生蛋白-7在幼年大鼠肾小管间质损伤中的表达及意义  

The Expression and Significance of Bone Morphogenetic Protein-7(BMP-7) in Renal Tissue During Tubulointerstitial Lesion in Young Rat with Unilateral Ureteral Obstruction

作　　者：王晓红[1] 马宏[1] 武艳[1] 李卫卫[1] 赵晓华[1] 王亚娟[1] 杨博博[1] 

机构地区：[1]山西医科大学第一医院儿科,太原030001

出　　处：《中国中西医结合肾病杂志》2009年第11期965-968,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山西医科大学第一医院青年基金资助项目(No.YQ0810)

摘　　要：目的:探讨单侧输尿管梗阻(UUO)幼年大鼠肾间质纤维化形成过程中骨形态发生蛋白-7(BMP-7)的表达趋势及其与转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)的相关关系;观察血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)的干预作用。方法:采用单侧输尿管结扎制备UUO模型。3～4周龄幼年Wistar雄性大鼠随机分为对照组、模型组和干预组。于实验第3、7、14、28天取大鼠8只处死。HE及Masson染色观察肾组织的病理改变;免疫组化半定量检测各组大鼠肾组织BMP-7、TGF-β1及α-SMA蛋白表达。了解BMP-7与TGF-β1、α-SMA、肾间质纤维化程度的关系。结果:随梗阻时间延长,模型组BMP-7表达逐渐下降,TGF-β1、α-SMA表达进行性增高,干预组BMP-7表达较模型组显著增加(P<0.05);TGF-β1、α-SMA表达较模型组明显减少(P<0.05)。模型组肾小管间质TGF-β1、α-SMA表达明显增高(P<0.05),BMP-7表达显著减少(P<0.05)。与模型组相比,干预组肾小管间质TGF-β1、α-SMA表达显著减少(P<0.05),而BMP-7表达显著增多(P<0.05)。BMP-7与TGF-β1、α-SMA、肾间质纤维化程度成负相关(r分别为-0.844、-0.787、-0.952,P均<0.01)。结论:BMP-7表达减少伴随着肾小管上皮细胞转分化出现,提示BMP-7可能具有维持小管上皮细胞表型作用。苯那普利联合氯沙坦可能通过下调TGF-β1、α-SMA蛋白的异常高表达,上调BMP-7蛋白的异常低表达,直接或间接负性调控肾小管上皮细胞转分化,阻止肾间质纤维化进展。Objective：To investigate the tendency of BMP-7 expression in the course of renal tubulointerstitial fibrosis with unilateral ureteral obstruction and the correlation of BMP-7 with tubulointerstitial damage,TGF-beta1 and α-SMA,and to evaluate the interfering effects with angiotensin converting enzyme inhibitor（ACEI） Benazepril and angiotensin-recepter blocks（ARB） Losartan.Methods：Three weeks＇ young male Wistar rats（n=96） were randomly divided into the control group,the model group and the intervention group.UUO model was induced by ligating the left ureter of rats.The eight rats were respectively sacrificed at the 3rd,7th,14th and 28th day. Pathological changes of the renal tissue were observed by HE and Masson staining,the protein expression of BMP-7,TGF-beta1,α-SMA were detected by immunohistochemical staining.Results：Renal BMP-7 protein levels progressively decreased during the progression of obstructive nephropathy.Compared with that in the UUO group,the level of BMP-7 protein was significantly increased in Benazepril combined with Losartan treatment group （P0.05）.The levels of TGF-β1 and α-SMA in UUO group were increased remarkably compared with those in the SOR（P0.05）.In Benazepril combined with Losartan treatment group,the levels of TGF-β1 and α-SMA were obviously decreased compared with those in the model group（P0.05）.The renal tubulointerstitial expression of BMP-7 was significantly correlated with expression of TGF-β1（r=-0.844,P0.01）,α-SMA（r=-0.787,P0.01） and tubulointerstitial injuryindex（r=-0.952,P0.01）.Conclusion：The decrease of BMP-7 and increase of TGF-β1 were correlated with the increased expression of α-SMA and the degree of interstitial lesions in obstructive nephropathy.This suggested that BMP-7 might block morphologic transformation of tubular epithelial cells,and TGF-β1 might induce EMT. Benazepril combined with Losartan treatment suppressed fibrosis,at least in part via down-regulating TGF-β1、α-SMA expression and up-regulating BMP-7

关 键 词：骨形态发生蛋白-7 转化生长因子-Β1 Α-平滑肌肌动蛋白 单侧输尿管梗阻 肾小管间质纤维化 

分 类 号：R692.6[医药卫生—泌尿科学]