齐墩果酸协同环孢素A延长大鼠移植肾的存活时间  

Oleanolic acid synergizes with cyclosporine A to prolong renal allograft survival in rats

作　　者：钱坤[1] 廖雯婷[2] 李建军[1] 蒋鸿涛[1] 周浩[1] 龙建华[1] 秦国庆[1] 王毅[1] 

机构地区：[1]南华大学附属第二医院肾移植中心,湖南衡阳421001 [2]南方医科大学病理学系,广东广州510515

出　　处：《南方医科大学学报》2014年第6期843-846,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(81172055)~~

摘　　要：目的观察齐墩果酸(OA)协同环孢素A(CsA)对大鼠移植肾存活的影响,探讨将齐墩果酸应用于肾移植术后免疫抑制治疗的临床价值。方法以BN大鼠为供体,LEW大鼠为受体,建立大鼠同种异体肾移植模型。将40只受体大鼠随机均分为对照组、OA组、CsA组、OA+CsA组,术前1 d开始进行干预。记录肾移植大鼠存活时间,并监测其血清肌酐浓度。术后第5天,免疫组化法检测移植肾CD4+和CD8+T细胞的浸润;多功能流式点阵仪(Luminex)检测以下因子的血清浓度:促炎细胞因子白介素-1β(IL-1β)、干扰素-γ(IFN-γ)、白介素-2(IL-2)、白介素-4(IL-4)、白介素-17(IL-17)和抗炎细胞因子白介素-10(IL-10),以及趋化因子单核细胞趋化蛋白-1(MCP-1)、干扰素诱导的蛋白-10(IP-10)、巨噬细胞炎性蛋白(MIP)和IFN-γ诱导的单核细胞因子(Mig);酶联免疫斑点法(ELISpot)检测表达IFN-γ、IL-10、IL-4和IL-17的T细胞频率。结果与其它各组比较,OA+CsA组的移植肾存活时间显著延长,浸润移植肾的CD4+和CD8+T细胞数量显著降低。与对照组比较,处理组的IL-1β、IP-10、MCP-1、Mig、MIP和IFN-γ、IL-17、IL-4的T细胞频率显著降低,但IL-10和IL-10的T细胞频率则显著升高。其中OA+CsA组较其他2个处理组的差异更为明显。结论 OA能协同CsA减轻肾移植大鼠排斥反应和炎症反应,延缓大鼠移植肾功能衰竭,延长大鼠移植肾存活时间。在临床肾移植领域,OA具有协同CsA促进移植肾存活的潜力。Objective To investigate the synergistic effect of oleanolic acid （OA） and cyclosporine A （CsA） on the survival of renal allografts in rats. Methods Renal allograft transplantation was performed using BN rats as donors and LEW rats as recipients. Forty male LEW rats were randomized into 4 equal groups for interventions with DMSO-PBS （control）, OA, CsA, or CsA＋OA, starting from 1 day before transplantation. Serum creatinine levels were regularly examined, and the survival of rats were recorded. On day 5 after transplantation, CD4 ＋ and CD8 ＋ T-cell infiltration in the renal grafts was analyzed by immunohistochemistry; the concentrations of the proinflammatory cytokines （IL-1β, IFN-γ, IL-2, IL-4, and IL-17）, anti-inflammatory cytokine IL-10 and chemokines （IP-10, MCP-1, MIP, and Mig） were analyzed with Luminex; the T-cell phenotypes （IFN-γ, IL-10, IL-4, and IL-17） were analyzed using ELISpot. Results In OA＋CsA group, renal allograft survival was markedly prolonged and CD4 ＋ and CD8 ＋ T cell infiltration in the graft significantly decreased as compared to other groups. A significant decrease in IL-2 was observed in OA group and OA＋CsA group, especially the latter. Compared with the control group, all the 3 treated groups showed significantly decreased IL-1β, IP-10 and MCP-1, increased IL-10 levels, decreased percentages of T cells secreting IFN-γ, IL-4 and IL-17, and increased percentage of T cells secreting IL-10. The increments of serum IL-10 level and T cell percentage were more prominent in OA＋CsA group than in the other two intervention groups. Conclusions OA and CsA synergistically ameliorate renal graft rejection and inflammation and promote allograft survival and function in rats.

关 键 词：齐墩果酸 环孢素A 肾移植 T淋巴细胞 细胞因子 趋化因子 

分 类 号：R699.2[医药卫生—泌尿科学]