Guo Hua, Zou Wanzhong
Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100083, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Oct;35(5):503-7.
To study the relationship between monocyte/macrophage (MC/MP) accumulation and tubulointerstitial fibrosis.
The renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were fed for 25 days. The kidneys were obtained every 5 days by killing the rats. The morphological changes of tubulointerstitial fibrosis were observed by light microscopy with HE, PAS, PASM and Masson staining. Immunohistochemistry and double immunohistochemistry were used to observe MC/MP accumulation and proliferation. In situ hybridization and immunochemistry were used to observe MCP-1 and M-CSF expression in experimental renal tissue. The MCP-1 protein expression was inspected by Western blot. All the data were analyzed statistically.
The pathological changes of tubulointerstitial fibrosis were typical. There were many MC/MPs accumulsated in the interstitial space at the early stage and some of them were PCNA positive. At the late stage both accumulation and proliferation of MC/MPs were decreased. The portion of monocyte proliferation was high correlated with the MC/MP accumulation. In situ hybridization showed the positive signals of MCP-1 and M-CSF were mainly located in the cytoplasm of degenerated tubular epithelium and they were strong at the early stage, weak at the late stage. MCP-1 by immunochemistry and Western blot were consistent with in situ hybridization. The MC/MP accumulation was high correlated with the expression of MCP-1 and tubular epithelium degeneration. The portion of monocyte proliferation was high correlated with the expression of M-CSF.
There was obvious accumulation of MC/MP at the early stage of tubulointerstitial fibrosis. The accumulation came from infiltration and proliferation which were regulated by degenerated tubular epithelial cells producing MCP-1 and M-CSF. MC/MP accumulation was highly correlated with tubular degeneration. MC/MP promoted tubulointerstitial fibrosis and damaged tubular epithelium by secreting a variety of cytokines.
研究单核细胞/巨噬细胞（MC/MP）积聚与肾小管间质纤维化之间的关系。
通过单侧肾静脉结扎建立Wistar大鼠肾小管间质纤维化模型。大鼠饲养25天。每隔5天处死大鼠获取肾脏。采用HE、PAS、PASM和Masson染色，通过光学显微镜观察肾小管间质纤维化的形态学变化。运用免疫组织化学和双重免疫组织化学观察MC/MP的积聚和增殖情况。采用原位杂交和免疫化学观察实验性肾组织中MCP-1和M-CSF的表达。通过蛋白质免疫印迹法检测MCP-1蛋白表达。所有数据进行统计学分析。
肾小管间质纤维化病理改变典型。早期间质中有大量MC/MP积聚，部分呈PCNA阳性。后期MC/MP的积聚和增殖均减少。单核细胞增殖比例与MC/MP积聚高度相关。原位杂交显示MCP-1和M-CSF阳性信号主要位于变性肾小管上皮细胞质中，早期强，后期弱。免疫化学和蛋白质免疫印迹法检测的MCP-1与原位杂交结果一致。MC/MP积聚与MCP-1表达及肾小管上皮细胞变性高度相关。单核细胞增殖比例与M-CSF表达高度相关。
肾小管间质纤维化早期MC/MP有明显积聚。积聚来源于浸润和增殖，受变性肾小管上皮细胞产生的MCP-1和M-CSF调控。MC/MP积聚与肾小管变性高度相关。MC/MP通过分泌多种细胞因子促进肾小管间质纤维化并损伤肾小管上皮细胞。
