CAJ | 학술논문

目的研究经他克莫司(Tac)处理的供者未成熟树突状细胞(imEX3)在延长大鼠移植心脏存活时间中的作用和机制.方法以Wistar大鼠为供者,SD大鼠为受者,行颈部异位心脏移植.心脏移植前将受者随机分为3组,每组15只,进行不同的预处理.第1组:为对照组,术前7 d经受者的尾静脉注射生理盐水1.0ml;第2组:为未经Tac处理组,术前7 d经受者的尾静脉注射未经Tac处理的imDC 2×106(1.0 m1);第3组:为Tac处理组,术前7 d经受者的尾静脉注射经Tac处理的imDC 2×106(1.0 m1).术后观察:移植心脏的存活时间、受者与供者及无关供者(Lewis大鼠)的单向混合淋巴细胞反应(MLR)、心肌组织病理学表现及血清中白细胞介素(IL)-2、IL-4、IL-10和γ干扰素(IFN-γ)的水平变化.结果第1、2、3组移植心脏的存活时间分别为(8.57±1.34)d、(20.92±2.68)d和(33.30±3.92)d.各组之间比较,差异均有统计学意义(P＜0.01);第2、3组受者对供者的MLR刺激指数较第1组明显降低,而对无关供者的MLR刺激指数则与第1组相近;各组受者血清IL-2、IFN-γ、IL-4、IL-10浓度问差异有统计学意义(P＜0.01),第3组IL-2和IFN-γ(代表TH1细胞)水平明显降低,而IL-4和IL-10(代表TH2细胞)水平明显增高.结论 imDC能够延长大鼠心脏移植后的存活时间,经Tac处理的imDC能够进一步加强这种作用;且imDC所诱导的免疫低反应性是供者特异性的.其机制可能主要与调节T淋巴细胞免疫应答类型(TH1至TH2的免疫偏移)和诱导T淋巴细胞免疫应答降低有关.
목적 연구경타극막사(Tac)처리적공자미성숙수돌상세포(imEX3)재연장대서이식심장존활시간중적작용화궤제.방법 이Wistar대서위공자,SD대서위수자,행경부이위심장이식.심장이식전장수자수궤분위3조,매조15지,진행불동적예처리.제1조:위대조조,술전7 d경수자적미정맥주사생리염수1.0ml;제2조:위미경Tac처리조,술전7 d경수자적미정맥주사미경Tac처리적imDC 2×106(1.0 m1);제3조:위Tac처리조,술전7 d경수자적미정맥주사경Tac처리적imDC 2×106(1.0 m1).술후관찰:이식심장적존활시간、수자여공자급무관공자(Lewis대서)적단향혼합림파세포반응(MLR)、심기조직병이학표현급혈청중백세포개소(IL)-2、IL-4、IL-10화γ간우소(IFN-γ)적수평변화.결과 제1、2、3조이식심장적존활시간분별위(8.57±1.34)d、(20.92±2.68)d화(33.30±3.92)d.각조지간비교,차이균유통계학의의(P＜0.01);제2、3조수자대공자적MLR자격지수교제1조명현강저,이대무관공자적MLR자격지수칙여제1조상근;각조수자혈청IL-2、IFN-γ、IL-4、IL-10농도문차이유통계학의의(P＜0.01),제3조IL-2화IFN-γ(대표TH1세포)수평명현강저,이IL-4화IL-10(대표TH2세포)수평명현증고.결론 imDC능구연장대서심장이식후적존활시간,경Tac처리적imDC능구진일보가강저충작용;차imDC소유도적면역저반응성시공자특이성적.기궤제가능주요여조절T림파세포면역응답류형(TH1지TH2적면역편이)화유도T림파세포면역응답강저유관.
Objective To study the effect of donor immature dendritic cells(imDCs)treated with Tacrolimus(TAC)on prolonging rat allograft survival and the action mechanism.Methods Cervical heart transplantations were performed in which Wister rats were used as donors,and SD rats as allograft recipients.Normal sodium(control group),imDCs(positive control group),and imDCs treated with TAG(TAC-treated group)were injected via vena caudalis 7 days before the operations respectively.Heart allograft survival was monitored and one-way MLR,heart pathology and the levels of IL-2,IL-4,IL-10,IFN-r in the serum were detected Results H test showed that there was high significant difference in heart allograft survival among the three groups(P＜0.01).Stimulation index in positive control and TAC-treated groups 2 and 3 in MLR was obviously lower than in control group,while stimulation index to independent donors in positive control and TAC-treated group were close to control group.Analysis of variance showed that there was high significant difference in serum concentrations of IL-2,IFN-r,IL-4,IL-10 among the three groups(P＜0.01).The concentrations of IL-2 and IFN-r being expressed on Thl were lower,and those of IL-4 and IL-10 being expressed on Th2 were obviously higher in positive control and TAC-treated groups.Conclusion ImDCs can prolong rat heterotopic cardiac allograft survival successfully;ImDCs treated with TAC can enhance the effect which is donor specific.ImDCs may induce the immune tolerance by means of modifying the immune response type of T cells(immune deflection from Th1 to Th2),and inducing T cells disenabling.