摘要
目的探讨联合输注受鼠调节性T淋巴细胞（Treg细胞）和供鼠未成熟树突状细胞（imDC）延长同种肝移植大鼠存活时间的作用。方法以DA大鼠为供鼠，Lewis大鼠为受鼠，采用改良二袖套法进行原位肝移植100例。采用随机数字表法将受鼠平均分为5组，急性排斥反应（AR）组、成熟树突状细胞（mDC）组、imDC组、Treg组及imDC＋Treg组受鼠分别于术前5d经尾静脉注射生理盐水、供鼠的miX；、供鼠的imDC、受鼠的Treg细胞及供鼠的imDC＋受鼠的Treg细胞。术后每组预留8只受鼠观察和记录存活时间。术后3、7、10d，检测各组肝功能指标，采用酶联免疫吸附试验法检测血清白细胞介素2（IL-2）、IL-10及转化生长因子β（TGF-β）的浓度；取各组受鼠移植肝组织进行病理学检查，采用原位末端标记法检测各组肝组织细胞的凋亡情况。结果与其他4组相比，imDC＋Treg组受鼠术后肝功能恢复明显较快；imDC＋Treg组术后7d时外周血ILq0和TGF-β浓度均升高，IL-2浓度降低。imDC＋Treg组移植肝组织仅有较少量的单核细胞浸润，属非确定型AR至轻度AR，术后10d开始出现肝细胞再生，有少量的中性粒细胞浸润；imDC＋Treg组肝组织汇管区淋巴细胞凋亡数量高于miX；组，肝脏汇管区淋巴细胞凋亡数量最多。imDC＋Treg组受鼠中位存活时间为37d，明显长于imDC组的23d和Treg组的15d（P〈0．05），AR组和mDC组受鼠存活时间均未超过12d。结论单独输注供鼠的imDC或受鼠的Treg细胞均未能诱导同种肝移植大鼠的长期存活；而联合输注受鼠的Treg和供鼠的irnDC能显著延长同种肝移植大鼠的存活时间。
Objective To explore the effects of combined infusion of Treg cells from recipient rats and imI）Cs from donor rats prolonging the survival time of rats undergoing allogeneic orthotopic liver transplantation. Methods One hundred cases of rat allogeneic orthotopie liver transplantation were performed by using modified two-cuff method： DA rats served as donors, and Lewis rats as recipients, which were divided into 5 groups： acute rejection group, mDC group, imDC group, Treg group, co-infusion group （imDC-Treg group）. 2 x 10＇ imDC, 2 x 106 mDC and 1 x 107 Treg cells were respectively injected to Lewis rats in every group via caudal vein before transplantation. Four Lewis rats from each group were randomly sacrificed on the day 3, 7 and 10 after transplantation. Liver function （ALT and TBIL） and changes of cytokines （IL 10, IL-2 and TGF-13） were evaluated in peripheral blood. The pathological changes of the liver graft were observed. The DNA fragmentation characteristics of apoptosis in the liver were detected by using TUNEL staining. Survival analysis was performed on remnant rats. Results The liver function in infl）C-Treg group had reverted to normal faster than that in the control groups. ELISA revealed that at day 7, the serum levels of IL-10 and TGF-β were higher, and the serum levels of IL-2 were lower in imDC Treg group. Liver pathology demonstrated that there was only a slight number of mononuclear cell infiltration in hepatic graft afterorthotopic liver transplantation in co-infusion group （1miX;-I reg group J, wmcn oelongea ro a identified＂ or ＂slight＂ type of acute rejection, and the liver graft showed regeneration of hepatocytes along with a small number of neutrophile granulocyte infiltration at the day 10. TUNEL staining indicated that the number of apoptotic T cells was much less in control groups than in imDC-Treg groups. The survival time of recipients in Treg-imDC group was 37 days, significantly longer than in imDC group （23 days） and Treg group （15 days）. Conc
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2012年第10期619-623,共5页
Chinese Journal of Organ Transplantation
基金
福建省自然科学基金重点项目（2009D066）
福建省自然科学基金（201lJ01162）
福建省属高校基金（JK2011021）
