CAJ | 학술논문

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。
목적：탐토CCL21/CCR7신호통로여이식신섬유화적관계。방법수집길림대학신이식중심78례신이식후기항수평상승환자적신장천자표본，채용상규소목소-이홍（HE）염색、Masson염색화PAS염색후진행병리진단，연후채용면역조화염색방법，관찰섬유모세포표면항원（FSP）、추화인자CCL21급기수체CCR7적분포화표체。결과 HE、Masson、PAS염색진단신천자표준적류형위급성배이반응13례，혈관배이반응6례，만성배이반응8례，교계성병변13례，신병복발4례，신소관손상2례，기타병변2례；상대정상30례。면역조화염색현시：급성배이반응자FSP표체고우상대정상자（P＜0.01），만성배이반응자고우이식교계성병변자화상대정상자（P＜0.05화P＜0.01），기타병변류형간FSP표체차이무통계학의의（균P＞0.05）。재염성세포다적조직구역섬유모세포적수량유증다추세。CCR7양성섬유모세포재만성배이반응자중유증다추세，CCR7재신천자조직적표체부위주요시혈관벽，재부분위축적신소관급간질중가견양성표체；CCL21주요표체우신소관상피세포화소량섬유모세포중。각병리분형환자FSP、CCR7、CCL21표체부위급양성비례비교차이무통계학의의（균P＞0.05）。CCL21화CCR7、FSP화CCL21적양성표체세포분별공표체우섬유모세포화신소관상피세포。결론섬유모세포적출현여염성세포유관，병사급성배이반응전변위만성배이반응적위험인소가대，CCL21/CCR7재이식신섬유화발생궤제중유중요작용。
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 were collected from kidney transplantation center of Jilin University,followed by the pathological diagnosis of the biopsy specimens using hematoxylin-eosin(HE)staining,periodic acid-Schiff(PAS)staining and Masson staining. Then the immunohistochemistry staining was performed to detect the expressions and localizations of FSP,CCL21, and CCR7 respectively. Results All cases were diagnosed by HE,Masson and PAS staining,which included 13 cases of 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 normal group(P<0.01),and the number of FSP+ interstitial cells in chronic rejection group were more than boundary lesion 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 statistical significance for the expression of FSP,CCR7 and CCL21 in all pathological groups(all P>0.05). The expressions of CCR7 and CCL21,FSP and CCL21 were observed in renal tubule and fibroblast. Conclusions Some cytokins can stimulate 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.