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目的:观察单侧输尿管梗阻(UUO)大鼠模型中骨形态形成蛋白-7(BMP-7)在肾小管间质中的表达部位、动态变化及其与肾间质纤堆化的 关系。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1d、3d、7d、14d处死大鼠,采用RT-PCR检测BMP-7mRNA、 转化生长因子-β1(TGF-β1)mRNA表达水平,用免疫组化检测肾小管间质中BMP-7、TGF-β1蛋白的定位和表达及其与输尿管梗阻后肾间质损害的关系。 结果:与时照组相比,BMP-7mRNA于术后第1天即出现表达下降并随梗阻时间延长递减,而TGF-β1mRNA则随着梗阻时间延长增加(P均<0.05)。BMP -7蛋白在对照组中高度表达,髓质区表达明显高于皮质区,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BMP-7蛋白表达呈进行性下 降,而TGF-β1蛋白表达则逐渐增加(P均<0.01)。结论:BMP-7蛋白于肾小管间质病变早期即出现表达下调,早于肾间质纤维化的出现,且随间质病变进 展进行性下降。BMP-7表达下调可能参与介导肾小管间质损害的发生发展。
OBJECTIVE: To observe the expression of BMP-7 in tubulointerstitium and its relationship with renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rat model. Methods: Sixty Wistar rats were randomly divided into normal rats group, sham operation group and unilateral ureteral obstruction group. Rats were sacrificed on the 1st, 3rd, 7th, and 14th day after operation. BMP-7 mRNA was detected by RT- The expression of TGF-β1 mRNA in renal tubulointerstitium was detected by immunohistochemistry and the relationship between the expression of BMP-7 and TGF-β1 protein and tubulointerstitial damage after ureteral obstruction was analyzed. Results: Compared with the control group, the expression of BMP-7 mRNA decreased on the first postoperative day and decreased with the prolongation of obstruction time, while the TGF-β1 mRNA increased with the prolongation of obstruction time (all P <0.05). BMP-7 protein was highly expressed in the control group, the medulla area was significantly higher than the cortex, mainly in the renal tubules and renal interstitium, glomerular basically no expression. The expression of BMP-7 in the obstructive group decreased progressively, while the expression of TGF-β1 increased gradually (all P <0.01). CONCLUSION: BMP-7 protein is downregulated in the early stages of tubulointerstitial lesions, earlier than the appearance of renal interstitial fibrosis, and progressively decreases with the progression of interstitial lesions. BMP-7 downregulation may be involved in the development of tubulointerstitial damage.