肾小球疾病中肾小管间质纤维化的研究  

The study of renal tubulointerstitial fibrosis in glomerular diseases

作　　者：李玲[1] 邹万忠[1] 张波[1] 刘玉春[2] 杨京平[1] 

机构地区：[1]北京大学医学部病理学系,100083 [2]北京大学第一医院肾内科

出　　处：《临床内科杂志》2003年第11期607-609,共3页Journal of Clinical Internal Medicine

摘　　要：目的　研究肾小球疾病中肾小管间质纤维化的发生机制。方法　通过对 44例病因、病理类型和肾功能损伤程度不同的原发性和继发性肾小球疾病的临床和病理分析研究 (包括硬化性肾小球肾炎 15例、结节性硬化性糖尿病肾病 10例 ,膜性肾病 19例 )肾小球、肾小管和肾间质的损伤 ,并进行TGFβ1、α SMA、Ⅰ、Ⅲ型胶原蛋白表达的回顾性分析 ,探讨它们与肾小管间质损伤之间的关系。结果　肾小球的损伤与肾小管间质纤维化密切相关 ;TGFβ1的表达位于损伤的肾小管上皮细胞 ,Ⅰ、Ⅲ型胶原和肌纤维母细胞 (α SMA阳性细胞 )主要位于增生的肾间质 ,其中 ,Ⅰ、Ⅲ型胶原还见于部分肾小管上皮细胞。它们的表达均与肾小管间质损伤程度相关。肾小管TGFβ1的表达还与肾间质肌纤维母细胞及Ⅲ型胶原的表达相关。肾间质肌纤维母细胞的表达又与肾间质Ⅰ、Ⅲ型胶原表达相关。结论　损伤的肾小管是肾小管间质纤维化的中心环节。受缺血缺氧、尿蛋白和尿糖损伤的肾小管上皮细胞通过自分泌和旁分泌的途径 ,产生多种细胞因子 (TGFβ1等 )和表型转化 (产生Ⅰ、Ⅲ型胶原等 ) 。Objective To investigate the pathogenesis of renal tubulointerstitial fibrosis in glomerular diseases.Methods Forty-four patients of primary and secondary glomerular disease with various etiology,pathological type and variable degree of renal insufficiency were retrospectively investigated.They consisted of 15 cases with sclerosing glomerulonephritis,10 cases with nodular diabetic glomerulosclerosis and 19 cases with membranous nephropathy.Clinicopathological analysis and immunohistochemistry stain were performed.The damage for glomeruli,tubules and renal interstitium,renal synthesis of TGFβ 1,collagenⅠand Ⅲ as well as myofibroblast(α-SMA positive cells)expression were also analyzed.The possible links of them with the degree of tubulointerstitial fibrosis and the relationship among them were evaluated.Results The glomerular lesions were associated with tubulointerstitial fibrosis.TGFβ 1 expression was testified in the damaged tubular epithelial cells.CollagenⅠ,Ⅲ and myofibroblasts mainly distributed in the proliferative interstitium(around atrophy tubule and fibrosis areas).The expression of TGFβ 1 was positively related to interstitial myofibroblast and collagen Ⅲ expression. In addition,there was a significant correlation between interstitial myofibroblast and interstitial collagenⅠ,Ⅲ expression.Conclusions The damaged tubular epithelial cell plays an important role in tubulointerstitial fibrosis.The impaired tubular epithelial cells undergo ischemia,hypoxia,toxicosis of albumen and glucose,produced cytokines(TGFβ 1 etc.)by autocrine and paracrine.The phenotypic transformation(synthesis and release of collagen Ⅰ,Ⅲ)was a key factor in the pathogenesis of tubulointerstitial fibrosis of human glomerular diseases.

关 键 词：肾小球疾病 TGFΒ1 Ⅰ型胶原 Ⅲ型胶原 α—SMA 

分 类 号：R692.6[医药卫生—泌尿科学]