骨形成蛋白7和转化生长因子β1在不同病理类型IgA肾病的变化

目的 观察转化生长因子β1（TGF-β1）和骨形成蛋白7（BMP-7）在不同病理类型IgA肾病的变化,并探讨其意义。方法 89例IgA肾病患者分成3组：A组为47例轻度系膜增生性IgA肾病;B组为29例中重度系膜增生性IgA肾病;C组为13例增生硬化或硬化性IgA肾病。检测患者的血压、尿蛋白量（24 h）、Scr和Ccr。免疫组化和ELISA方法测定患者肾组织冰冻切片及其血、尿中TGF-β1和BMP-7水平。计算患者病理切片硬化肾小球数、新月体数和间质纤维化面积百分比。结果 随着IgA肾病患者肾小球病变的加重,肾小管萎缩和肾间质纤维化增多,其血压、尿蛋白量（24 h）、Scr逐渐增加,除B、C两组间尿蛋白量（24 h）无显著差异外,其余各组间差异均有统计学意义（P＜0．05）。与A组比较,B组肾组织及血、尿TGF-β1明显增多,C组显著降低（P＜0．01）。肾组织冰冻切片及血、尿BMP-7随着肾脏病变的加重,水平逐渐下降（P＜0．01）;而且与Ccr呈正相关;与血压、Scr、尿蛋白量（24 h）、硬化肾小球数、新月体数、肾间质纤维化面积呈负相关。结论 TGF-β1在IgA肾病系膜增生严重时明显增加,肾脏广泛纤维化时明显降低,可能参与了IgA肾病肾间质纤维化的发生。BMP-7随肾脏病变的加重而明显降低,可能导致其抗肾纤维化作用减弱。

Role of transforming growth factor β1 and bone morphogenetic protein 7 in IgA nephropathy

Objective To investigate the effects of transforming growth factor β1(TGF-β1) and bone morphogenetic protein 7 (BMP-7) in IgA nephropathy(IgAN). Methods The study included 47 mild mesangial proliferative IgAN (group A) cases, twenty nine moderate and severe mesangial proliferative IgAN (group B) cases and thirteen proliferative-sclerosing or sclerosing IgAN (group C) cases. Blood pressure, 24 h urinary protein, serum creatinine and Ccr were monitored. Levels of TGF-β1 and BMP-7 in serum and urine were measured by ELISA. The expression of TGF-β1 and BMP-7 in renal frozen setions was examined by immunohistochemistry. The ratios of sclerosing glomeruli, crescents and area of interstitial fibrosis were calculated. Results Glomerular demage was positively correlated to atrophy tubule and interstitial fibrosis, the levels of blood pressure, 24 h urinary protein and serum creatinine. As for the above parameters, each group had significant difference（P < 0.05）except 24 h urinary protein between group B and C. Compared to Group C, levels of TGF-β1 in serum and urine were much higher in group A and B.（P < 0.01）. The level of BMP-7 in serum and urine was gradually decreased with the progression of renal damage (P < 0.01), and it was positively correlated with Ccr, and negatively correlated with blood pressure, proteinuria excretion rate, glomerular sclerosis, crescent and tubulointerstitial fibrosis. Conclusions TGF-β1 is up-regulated in early stage of mesangial proliferation while down-regulated in renal fibrosis, suggesting TGF-β1 may take part in renal fibrosis. The level of BMP-7 is gradually reduced with the progression of renal damage, leading to the inhibition of its protection against renal fibrosis.