摘要
目的探讨骨化三醇和氨基胍(AG)联合应用对大鼠肾移植急性排斥反应的作用。方法选取清洁级近交系健康雄性Wistar大鼠和SD大鼠为供、受者。实验随机分为5组,每组10只。Ⅰ组为同基因对照组:Wistar大鼠肾脏移植给Wistar大鼠,术前和术后不做任何处理;其余各组均为异基因移植,Wistar大鼠肾脏移植给SD大鼠,Ⅱ组为排斥对照组:术前和术后不做任何处理;Ⅲ组为氨基胍治疗组:手术当日开始腹腔注射氨基胍200mg/kg,2次/d,至实验结束;Ⅳ组为骨化三醇治疗组:术前1d开始腹腔注射骨化三醇1μg·kg-1·d-1,至实验结束;Ⅴ组为联合治疗组:氨基胍和骨化三醇联合应用,给药方案同Ⅲ、Ⅳ组。观察各组受者生存期和移植后5d肾组织病理学变化,检测血清肌酐、尿素氮、钙、磷以及γ干扰素(IFNγ)含量。结果Ⅰ～Ⅴ组受者存活时间分别为(9.1±1.9)d、(5.3±0.8)d、(9.7±2.1)d、(8.6±1.6)d和(12.9±3.4)d。Ⅴ组较Ⅱ～Ⅳ组生存期延长,差异有统计学意义(P<0.05)。Ⅲ、Ⅳ组受者存活期、移植肾排斥反应程度、肾功能及血清IFNγ表达水平较Ⅱ组明显改善或降低(P<0.01),Ⅴ组又较Ⅲ、Ⅳ效果更佳(P<0.05)。结论同种异体原位肾移植后联合应用用骨化三醇和氨基胍治疗可有效预防急性排斥反应,二者有明显的协同作用。
Objective To explore the methods of induced tolerance in rats renal allotransplantation and provide a theoretical basis for clinical use. Methods Orthotopic renal transpl antation fromWistar rats to SD rats was used as a model of study. The experimental rats were divided into the following groups： Group Ⅰ as isotransplantation control group, Ⅱ as acute rejection control group, respectively. Group Ⅲ , Ⅳ and Ⅴ were treated with aminoguanidine （AG）, calcitriol and the combined use of calcitriol and AG, respectively. The survival time of recipients was observed, meanwhile, the donor specific mixed lymphocyte reaction （MLR） and concentrations of IFN-γ, Ca^2＋ and p^3＋ in serum were measured. HE staining inspected all specimens of kidney grafts. Results The recipient survival time in the groups Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ were （9. 1 ± 1.9）, （5.3 ± 0. 8）, （9. 7 ± 2. 1 ）, （8. 6 ± 1.6）and（12. 9 ± 3. 4）days, respectively. There was significant difference in recipient survival time between group Ⅴ and group Ⅱ, Ⅲ and Ⅳ （P〈0.01 vsgroup Ⅱ and Ⅳ, P〈0.05 vs group Ⅲ）. Five days after operation, the proliferation of anergic cells in the MLR was strongly inhibited （P〈0. 01）, and the level of IFN-γ in serum was obviously decreased （P〈0. 01）. The recipients＇ renal function was obviously improved （P〈0. 01 ） and the grades of acute rejection of allgrafts were mitigated （P〈0.05）, in groups Ⅲ, Ⅳ and Ⅴ as compared with group Ⅱ. The results of group V were more satisfactory than in group Ⅲ and group Ⅳ. The levels of Ca^2＋ and P^3＋ in serum had no significant difference among them. Conclusion Calcitriol and AG have a synergistic effect and can achieve better effects on the inducement of immunological tolerance and the improvement of graft survival.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2005年第8期494-496,共3页
Chinese Journal of Organ Transplantation
