Abstract:

Objective To explore the role of CCL21/CCR7 signaling pathway in renal allograft fibrosis. Methods Specimens from 78 patients with creatinine increasing after kidney transplantation werecollected from kidney transplantation center of Jilin University，followed by the pathological diagnosis of the biopsyspecimens using hematoxylin-eosin（HE）staining，periodic acid-Schiff（PAS）staining and Masson staining. Thenthe immunohistochemistry staining was performed to detect the expressions and localizations of FSP，CCL21, andCCR7 respectively. Results All cases were diagnosed by HE，Masson and PAS staining，which included 13 casesof acute rejection，6 cases of vascular rejection，8 cases of chronic rejection，13 cases of boundary lesion，4 cases of nephropathy relapse，2 cases of tubular lesion，2 cases of other lesion and 30 cases of normal. Immunohistochemistry staining showed that the number of FSP+ interstitial cells in acute rejection group were more than relative normalgroup（P ＜ 0.01），and the number of FSP+ interstitial cells in chronic rejection group were more than boundarylesion group and relative normal group（P ＜ 0.05 and P ＜ 0.01）. There was no statistical significance in FSP + interstitial cells among other types of pathological changes（all P ＞ 0.05）. The result showed that the number of fibroblast in inflammatory areas were more than other areas. CCR7 positive fibroblast cells had increased terndency in chronic rejection group. CCR7 were observed in wall of blood vessel and some atrophic renal tubule and renal interstitium. CCL21 were observed in renal tubular epithelial cells and some fibroblast cells. There were no statisticalsignificance for the expression of FSP，CCR7 and CCL21 in all pathological groups（all P ＞ 0.05）. The expressionsof CCR7 and CCL21，FSP and CCL21 were observed in renal tubule and fibroblast. Conclusions Some cytokins canstimulate the cytoactivity of fibroblast in inflammation microenvironment. Patients who underwent the acute rejection in early stage after allograft kidney transplantation are more likely to suffer the reoccurrence of the chronic rejection than those who don't . CCR7/CCL21 signaling has important role in fibrosis of allograft kidney.

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摘要：

目的 探讨 CCL21/CCR7 信号通路与移植肾纤维化的关系。方法 收集吉林大学肾移植中心78 例肾移植后肌酐水平上升患者的肾脏穿刺标本，采用常规苏木素 - 伊红（HE）染色、Masson 染色和 PAS 染色后进行病理诊断，然后采用免疫组化染色方法，观察纤维母细胞表面抗原（FSP）、趋化因子 CCL21 及 其受体 CCR7 的分布和表达。结果 HE、Masson、PAS 染色诊断肾穿刺标准的类型为急性排异反应 13 例， 血管排异反应 6 例，慢性排异反应 8 例，交界性病变 13 例，肾病复发 4 例，肾小管损伤 2 例，其他病变 2 例；相对正常 30 例。免疫组化染色显示 ：急性排异反应者 FSP 表达高于相对正常者（P ＜ 0.01），慢性排异反 应者高于移植交界性病变者和相对正常者（P ＜ 0.05 和 P ＜ 0.01），其他病变类型间 FSP 表达差异无统计学意义（均 P ＞ 0.05）。在炎性细胞多的组织区域纤维母细胞的数量有增多趋势。CCR7 阳性纤维母细胞在 慢性排异反应者中有增多趋势，CCR7 在肾穿刺组织的表达部位主要是血管壁，在部分萎缩的肾小管及间质 中可见阳性表达 ；CCL21 主要表达于肾小管上皮细胞和少量纤维母细胞中。各病理分型患者 FSP、CCR7、 CCL21 表达部位及阳性比例比较差异无统计学意义（均 P ＞ 0.05）。CCL21 和 CCR7、FSP 和 CCL21 的阳性 表达细胞分别共表达于纤维母细胞和肾小管上皮细胞。结论 纤维母细胞的出现与炎性细胞有关，并使急性排异反应转变为慢性排异反应的危险因素加大，CCL21/CCR7 在移植肾纤维化发生机制中有重要作用。

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