实验性肾小管间质纤维化中肾小管上皮细胞表型转化的研究  

Transdifferentiation of tubular epithelial cells in tubulointerstitial fibrosis

作　　者：郭华[1] 邹万忠[1] 

机构地区：[1]北京大学医学部病理学系,100083

出　　处：《中华病理学杂志》2003年第4期364-367,共4页Chinese Journal of Pathology

基　　金：国家自然科学基金资助项目 (3 9770 2 93 )

摘　　要：目的　观察和研究肾小管间质纤维化过程中肾小管上皮细胞发生表型转化的现象及其形态特点。方法　结扎大鼠一侧肾静脉 ,制作大鼠肾小管间质纤维化模型 ,连续饲养 2 5d。每 5d杀检 5只 ,对肾脏重点检查 ,未结扎肾静脉的对侧肾作为对照 ,采用光镜、透射电镜、偏振光显微镜及免疫组织化学方法 [链霉素抗生物素蛋白 过氧化物酶 (SP)法 ]观察肾组织的病理变化以及肾小管上皮细胞的表型转化情况。结果　肾静脉结扎侧肾逐渐出现肾小管萎缩 ,肾间质淋巴、单核细胞浸润和纤维化等肾小管间质纤维化的典型病变。免疫组织化学观察发现 ,随着病变的发展 ,损伤的肾小管上皮细胞角蛋白表达逐渐减弱 ,而α平滑肌肌动蛋白、波形蛋白、转化生长因子 β1和Ⅰ、Ⅲ型胶原的表达逐渐增强 ,肾间质中也出现角蛋白阳性的间质细胞。透射电镜下可见肾小管上皮细胞内线粒体减少 ,内质网和微丝增多 ,并可见肾小管上皮细胞突破基底膜游离到肾间质中。天狼星红染色偏振光显微镜观察显示早期肾间质中Ⅲ型胶原增生为主 ,后期以Ⅰ型胶原为主。结论　在大鼠肾小管间质纤维化病变的发生和发展中 ,肾小管上皮细胞可转化为间质成纤维细胞 。Objective To observe the transdifferentiation of renal tubular epithelial cells in tubulointerstitial fibrosis. Methods The renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were kept 25 days after renal vein ligature. The kidneys were dissected every 5 days by killing 5 rats. The morphological changes of the kidney were observed by light microscopy, electron microscopy, polarizing microscopy and immunohistochemistry method. Results The histological changes showed tubular atrophy and disappearance, widening of intertubular spaces with increased lymphocytes and mononuclear cells infiltration and fibrosis. The CK marker in injured and atrophic epithelial cells gradually weakened, but the α-SMA, vimentin, TGF-β 1, collagen Ⅰ and Ⅲ showed gradually stronger positivity for immunohistochemistry. Some interstitial cells became positive for CK. Electron microscopy revealed decreased mitochondria, increased endoplasmic reticulum and microfilament of the tubular epithelial cells which merged into the interstitium. During the early stage of tubulointerstitial fibrosis, there was proliferation of type Ⅲ collagen and then followed by type Ⅰ collagen at later stage when observing the Sirius Red stained sections under the polarizing microscope. Conclusion Tubular epithelial cells can transdifferentiate to fibroblasts during the process of tubulointerstitial fibrosis.

关 键 词：肾小管 间质纤维化 上皮细胞 表型转化 大鼠 成纤维细胞 

分 类 号：R692.6[医药卫生—泌尿科学]