Oleanolic Acid, a plant triterpenoid, significantly improves survival and function of islet allograft.
Oleanolic Acid, a plant triterpenoid, significantly improves survival and function of islet allograft.
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DOI：
10.1097/tp.0b013e3181b9cbc4
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发表时间：
2009-10-27
期刊：
影响因子：
6.2
通讯作者：
Mohanakumar T
中科院分区：
文献类型：
--
作者：
Nataraju A;Saini D;Ramachandran S;Benshoff N;Liu W;Chapman W;Mohanakumar T
油酸（OA）是一种普遍存在的三萜类化合物，具有有效的抗氧化和抗炎特性。在这里，我们测试了OA的这些组合特性是否可以预防归因于移植物排斥的非免疫原发性无功能和免疫现象，从而延长胰岛移植物存活。用BALB/c胰岛移植于STZ诱导的糖尿病C57 BL/6小鼠肾被膜下。接受者用0.5mg/天的OA腹膜内处理。两天收集一次血清样品，并用于Luminex、ELISA和供体特异性抗体筛选。在不同的时间间隔处死移植小鼠，获得脾细胞和肾脏样品，分别用于ELISPOT，MLR和免疫组织化学研究。骨关节炎组小鼠移植后2± 1d血糖下降明显快于未治疗组（4±2）d。OA使移植胰岛的存活时间延长至23±3天，甚至在250个胰岛的情况下也逆转了糖尿病。治疗组血清IL-10升高2倍，IP-10和IL-4降低3倍。在ELISPOT中发现产生IFNγ（4.5倍）、IL-4（3.5）、IL-2（2.3）和IL-17（4）的T细胞群的频率显著降低。OA处理的移植物具有显著减少和延迟的CD 4+和CD 8 + T细胞浸润。OA也延迟供体特异性抗体的产生长达19天移植后。CSA、OA联合治疗使移植胰岛存活时间进一步延长至34 ± 3天。总之，OA是一种有吸引力的，膳食无毒植物三萜类化合物，它抑制促炎细胞因子的产生，并延迟移植物特异性免疫反应，以延长胰岛移植物存活。
Oleanolic acid (OA) is a ubiquitous triterpenoid, with potent anti-oxidant and anti-inflammatory properties. Here we tested if these combined properties of OA can prevent non-immunologic primary nonfunctioning and immunologic phenomena ascribed to graft rejection hence prolong islet allograft survival. Islet transplants were performed under kidney capsule of STZ induced diabetic C57BL/6 mice with BALB/c islets. Recipients were treated with 0.5mg/day of OA i.p. serum samples were collected once in two days and used for luminex, ELISA and donor specific antibody screening. Transplanted mice were sacrificed at different time intervals to obtain splenocytes and kidney samples for ELISPOT, MLR and immunohistochemical studies respectively. Post-transplant the decrement of blood glucose was significantly faster in mice receiving OA <2±1days compared to untreated (4±2). OA prolonged survival of transplanted islets up to 23±3 days, and reversed diabetes even with 250 islets. Treatment group showed increased serum IL-10(2fold) and decreased IP-10 and IL-4(3) in luminex. Significantly reduced frequency of IFNγ(4.5fold) IL-4(3.5), IL-2(2.3) and IL-17(4) producing T cell populations were found in ELISPOT. OA treated grafts had significant reduced and delayed infiltration of CD4+ and CD8+ T cells. OA also delayed donor specific antibody generation up to 19 days following transplantation. Combined treatment with CSA, OA further prolonged the islet allograft survival to 34 ± 3 days. In conclusion OA is an attractive, dietary non-toxic plant triterpenoid, which suppresses the production of pro-inflammatory cytokines and delays graft specific immune responses to prolong islet allograft survival.