摘要
目的观察大鼠肾小管间质纤维化过程中,肾小管上皮细胞是否发生表型转化。方法以腺嘌呤150 mg·kg-1·d-1灌胃,连续17周,制作大鼠肾小管间质纤维化模型。采用光镜、透射电镜、偏振光显微镜及免疫组织化学等方法,观察病变肾组织的病理变化以及肾小管上皮细胞的表型转化情况。结果病变肾组织出现肾小管变性、萎缩和再生,肾间质淋巴和单核细胞浸润以及进行性肾间质纤维化等肾小管间质纤维化的典型的病变。偏振光显微镜观察发现,随着病变的进展,间质中以Ⅲ型和Ⅰ型胶原为主的大量胶原纤维增生,并逐渐加重。免疫组化结果显示,损伤的肾小管上皮细胞处于萎缩和再生状态,随着病变的进展,小管上皮细胞内逐渐出现d平滑肌肌动蛋白(α-SMA)和波形蛋白(vimentin)的阳性表达。透射电镜下可见肾小管上皮细胞内原纤维出现以及突破基底膜游离到肾间质中,并与肾间质中的间质细胞、胶原纤维相混合存在。结论在大鼠肾间质纤维化的发生过程中,受损并处于再生状态的肾小管上皮细胞有向肌成纤维细胞等间胚叶细胞转化并产生细胞外基质的功能。
Objective To observe the phenotypic changes between renal tubular epithelial cells and mesenchymal cells in rat tubulointerstitial fibrosis(TIF) .Methods The renal tubulointerstitial fibrosis models of Wistar rats were established by gavage with excessive adenine. The morphological changes of model kidney were observed by light microscopy, electron microscopy, polarizing microscopy. Theα-smooth muscle actin(a-SMA), vimentin, and keratin were examined by immunohistochemistry staining. While the proliferating cell nuclear antigen (PCNA) was also assessed. Results There were many 2, 8-dioxyadenine crystals derived from the metabolite of adenine to deposit in the renal tubules, which induced the injury. Tubular epithelial cells degeneration and regeneration, loss of renal tubules, mononuclear cells infiltration in renal interstitium and the accumulation of extracellular matrix protein were observed. Both α-SMA and vimentin were positive in some of renal tubules. And consecutive sections of immunohistochemical staining showed that the area of distribution of a-SMA positive cells was almost the same area as that of vimentin positive cells. Polarizing microscopy results showed that there was a mass of interstitial collagen ( Ⅲ and Ⅰ) accumulation. And electron microscopy examination proved that epithelial cells invaded into the renal interstitium. Conclusion There is tubular epithelial cells-myofibroblasts transdifferentiation in the process of TIF, and which plays a key role in the accumulation of extracellular matrix.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2003年第1期10-14,共5页
Chinese Journal of Nephrology
