转化生长因子β1在人多囊肾病发病中的作用  

Role of transforming growth factorβ1 in pathogenesis of human polycystic kidney disease

作　　者：汤兵[1] 梅长林[1] 孙田美[1] 张玲[2] 章建全[2] 宋吉[1] 沈学飞[1] 王文靖[1] 吴玉梅[1] 

机构地区：[1]第二军医大学长征医院解放军肾脏病中心,上海200003 [2]第二军医大学长征医院超声诊断科,上海200003

出　　处：《医学研究生学报》2005年第9期793-796,799,i0011,共6页Journal of Medical Postgraduates

基　　金：国家"十五"重大科技专项基金资助项目(批准号:2002AA2Z3130);国家自然科学基金资助项目(批准号:30170901;30271523)

摘　　要：目的:研究转化生长因子β1(TGF-β1)在常染色体显性遗传性多囊肾病(ADPKD)患者中的表达分布特点,探讨其在ADPKD发病机制中的意义。方法:应用亲合素-生物素-过氧化物酶复合物(ABC)酶联免疫吸附法(ELISA)测定39例ADPKD患者的血浆、尿液及囊液中TGF-β1浓度;采用原位杂交和免疫组化方法检测TGF-β1、TGF-βⅠ型受体(TβRⅠ)、Ⅱ型受体(TβRⅡ)、结缔组织生长因子(CTGF)蛋白以及mRNA在正常肾及9例ADPKD患者肾组织中的表达分布特点,探讨其表达与肾间质纤维化程度的关系。结果:体液中血浆TGF-β1水平最高,ADPKD组为(15.12±8.53)μg/L、单纯性囊肿组为(11.43±8.93)μg/L,均显著高于正常对照组的(5.41±1.31)μg/L(P<0.05及P<0.01)。在ADPKD尿液中为(0.35±0.25)μg/(L.Cr)和囊液中为(0.31±0.21)μg/L,亦可检测出较低浓度的TGF-β1。在ADPKD患者肾组织中TGF-β1、TβRⅠ、TβRⅡ、CTGF蛋白及mRNA的表达较正常肾组织明显增加(P均<0.05),主要分布在萎缩的肾小管、间质血管周围及囊壁细胞。肾间质纤维化的程度与TGF-β1 mRNA(r=0.51,P=0.001)和蛋白(r=0.52,P=0.001)的阳性表达及CTGF mRNA(r=0.53,P=0.005)和蛋白(r=0.49,P=0.003)的阳性表达均呈明显正相关。结论:肾局部和循环中的TGF-β1在人ADPKD肾间质纤维化的进展中起一定作用。Objective ：To investigate characteristic expression of TGF-β1 in human ADPKD and clarify its role in the development and progression of human ADPKD. Methods ： Cyst fluid, urinary and plasma TGF-β1 levels were determined by ELISA in 39 ADPKD patients. The results were compared with those of normal subjects and of patients with simple renal cyst. TGF-β1, TGF-β1 receptors types Ⅰ , types Ⅱ , CTGF mRNA and proteins in the kidneys of human ADPKD were examined by in situ hybridization and immunohistochemistry. The relationship of the above fibrosing-associated indicators with the degree of interstitial fibrosis was analyzed. Results：Plasma TGF-β1 level was the highest among body fluids. In ADPKD and simple renal cyst, TGF-β1 levels were significantly higher than those in normal subjects （15.12 ±8.53）μg/L vs （5.41 ±1.31） μg/L,P〈0.01）; （11.43±8.93）μg/L vs （5.41± 1.31 ）μg/L,P 〈0.05）. TGF-β1 occured in urine and cyst fluid at lower levels in ADPKD group. Expression of TGF-β1, TGF-β1 receptors types Ⅰ , types Ⅱ , CTGF mRNA and proteins in the kidneys of ADPKD were significantly higher than those in the normal subjects （P 〈 0.05 ）. Expression of TGF-β1, TGF-β1 receptors types Ⅰ, types Ⅱ , CTGF mRNAs and proteins was upregulated in fibrotic interstitia, tubular epithelial cells and some sclerotic glomeruli. In cyst lining-epitheliar cells and vessel smooth muscle cells, the positive signals were most obvious. The degree of interstitial fibrosis was significantly correlated with TGF-β1 mRNA （ r = 0. 51, P = 0. 001 ） and proteins （ r = 0. 52, P = 0.001 ）, and also significantly correlated with CTGF mRNA （ r = 0. 53, P = 0.005 ） and proteins （ r = 0. 49, P = 0.003 ） too. Conclution：The results suggest that local and circulating TGF-β1 have a role in the development of interstitial fibrosis in human ADPKD.

关 键 词：多囊肾病 常染色体显性遗传 转化生长因子Β1 转化生长因子Β受体 结缔组织生长因子 肾间质纤维化 

分 类 号：R692[医药卫生—泌尿科学]