大鼠尿酸性肾病肾小管上皮细胞凋亡、增殖、表型转化及转化生长因子β1表达关系

RENAL EPITHELIAL CELL APOPTOSIS,PROLIFERATION,TRANSDIFFERENTATION AND TGFβ1 EXPRESSION IN RAT URIC ACID NEPHROPATHY

采用腺嘌呤灌胃法建立了大鼠实验性尿酸肾病动物模型,应用原位末端标记(TUNEL法)、免疫组化、原位杂交检测了6例正常及30例模型大鼠肾组织肾小管凋亡、增殖、表型转化现象及促纤维化细胞因子TGF-β1蛋白及基因表达状况.研究发现:尿酸性肾病发生发展过程中,肾小管上皮细胞存在明显的凋亡、增殖及表型转化现象.伴随着肾小管间质纤维化的形成,损伤肾小管凋亡、增殖、表型转化与转化生长因子β1(TGF-β1)表达呈增高趋势,且阳性表达细胞分布趋势一致:多位于尿酸盐沉积处损伤及再生的肾小管上皮细胞,可见凋亡、增殖、表型转化及转化生长因子β1表达在肾小管上皮细胞间伴随发生的现象.在病变晚期,肾小管明显萎缩及扩张,肾间质异物肉芽肿形成及弥漫纤维化,肾小管上皮细胞凋亡、增殖、表型转化及转化生长因子β1表达数量随残存肾小管上皮细胞的减少而呈下降趋势,但仍可见凋亡、增殖、表型转化及转化生长因子β1表达在肾小管上皮细胞间伴随发生的现象.这些结果均表明尿酸性肾病致肾小管间质纤维化过程中,肾小管上皮细胞凋亡、增殖、表型转化是损伤肾小管上皮细胞的重要病理变化形式,肾小管上皮细胞通过增殖,完成损伤肾小管的再生;通过细胞凋亡,清除坏死细胞并抑制肾小管上皮细胞的过度增殖;增殖的肾小管上皮细胞通过表型转化及TGFβ1表达,成为细胞外基质和促纤维化细胞因子的重要来源细胞,在肾小管间质纤维化中发挥了核心作用.

A model of rat uric acid nephropathy was established in 36 Wistar rats by stomach infusion of adenine. Epithelial cell apoptosis, proliferation, transdifferentation and TGSβ1 expression in normal and injured renal tubules were examined by electon microscopy, TUNEL staining, immunohistochemistry and in situ hybridization. Results： Epithelial cell apoptosis, proliferation, transdifferentation and TGFβ1 expression in renal tubules were noted in rat with uric acid nephropathy. There was significant correlation between apoptosis, proliferation, transdifferentation and TGF expression in renal tubules, which increased with duration of gastroperfusion. These positive signals are nearly at the same position of injured tubules in which uric acid crystals deposited. The injured tubule showed atrophy and dilation at end stage of uric acid nephropathy, apoptosis, hyperplasia, transdifferentation and TGF were lower, but rather similar to injured tubules. Conclusions： apoptosis, hyperplasia, and transdifferentation are important pathological changes in rat uric acid nephropathy and tubulointerstitial fibrosis.