骨形态形成蛋白-7及其受体在单侧输尿管梗阻大鼠模型中表达的研究

目的：探讨单侧输尿管梗阻（UUO）大鼠模 型不同时点肾脏中骨形态形成蛋白-7（BMP-7）及其受体BMPR-Ⅱ、ALK-2、ALK-3、ALK-6 mR NA表达水平的动态变化及意义。方法:60只Wistar大鼠随机分为正常大鼠 组、假手术组和单侧输尿管梗阻组，分别于术后1 d、3 d、7 d、14 d处死，采用RT-PCR方 法检测肾组织BMP-7、BMPR-Ⅱ、ALK-2、ALK-3、ALK-6的mRNA表达水平，免疫组织化学方法 检测肾小管间质中BMP-7的蛋白定位和表达。结果:与对照组相比，输尿 管梗阻组肾组织BMP-7及其受体BMPR-Ⅱ、ALK-2、ALK-3的mRNA表达于术后第1 d即出现下降 并随梗阻时间延长递减，而ALK-6的mRNA表达水平变化不明显。免疫组化结果显示BMP－7蛋 白在对照组中高度表达，主要分布在肾小管及肾间质，肾小球内基本无表达。在梗阻组随梗阻时间延长、肾间质损害加重，BMP－7蛋白表达呈进行性下降。结论:在肾间质损害过程中BMP-7及其受体BMPR-Ⅱ、ALK-2、ALK-3于病变早期即出现表达下调，早于肾间质纤维化病理改变的出现，BMP-7及其受体表达下调可能参与介导肾小管间质纤维化的发生发展。

Expression of BMP-7 and its receptors in rats with unilateral ureteral obstruction

AIM:To explore the expression changes of b one morphogenetic protein-7 (BMP-7) and its receptors (BMPR-Ⅱ,ALK-2,ALK-3,A LK-6) in the renal tubulo-interstitial lesions induced by unilateral ureteral ob struction (UUO).METHODS:Rats were divided into normal control,sham operation a nd UUO groups,and sacrificed at postoperative day 1,3,7 and 14.The mRNA leve ls of BMP-7,BMPR-Ⅱ,ALK-2,ALK-3 and ALK-6 were examined by RT-PCR.The protei n expression site and level of BMP-7 was detected by immunohistochemistry staini ng.RESULTS:Compared to sham operation group,the mRNA levels of BM P-7,BMPR-Ⅱ,ALK-2 and ALK-3 were significantly decreased,but the change of AL K-6 mRNA was not marked in UUO rats.The reduction of mRNA expression levels of BMP-7,BMPR-Ⅱ,ALK-2 and ALK-3 in the kidney tissue aggravated along with the d elayed post-operated days.The results of immunohistochemistry staining indicate d that BMP-7 mainly expressed in renal tubular and interstitial,rarely in glome ruli.In UUO rats,the protein expression of BMP-7 decreased in varying degrees according to the post-operated days.CONCLUSION:The loss of BMP-7 and its receptors (BMPR-Ⅱ,ALK-2,ALK-3) were observed in the early phase of fibrotic process and this may play a very important role in mediating the renal tubulointerstital fibrosis.