Bilirubin protects grafts against nonspecific inflammation-induced injury in syngeneic intraportal islet transplantation
Bilirubin protects grafts against nonspecific inflammation-induced injury in syngeneic intraportal islet transplantation
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胆红素在同基因门静脉内胰岛移植中保护移植物免受非特异性炎症诱导的损伤
DOI：
10.3858/emm.2010.42.11.075
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发表时间：
2010-11
影响因子：
12.8
通讯作者：
Jiang, Hongchi
中科院分区：
文献类型：
--
作者：
Wang, Jizhou;Ma, Yong;Pan, Shangha;Zhu, Huaqiang;Sun, Xueying;Reddy, Shiva;Jiang, Hongchi
非特异性炎症反应是门静脉内胰岛移植（IPIT）早期移植物失败的主要原因。胆红素是血红素催化剂的天然产物，具有抗氧化和抗炎活性。目前的研究表明，胆红素通过抑制非特异性炎症反应在同系大鼠模型的IPIT保护胰岛移植物。在体外试验中，通过将培养的大鼠胰岛素瘤INS-1细胞暴露于细胞因子（IL-1β、TNF-α和IFN-γ）来模拟炎症诱导的细胞损伤。在适当的低浓度下，胆红素可显著减轻细胞因子诱导的INS-1细胞活力下降和细胞凋亡，保护INS-1细胞的胰岛素分泌功能。链脲佐菌素诱导的糖尿病近交系雄性刘易斯大鼠接受不同胰岛当量（IEQ）的IPIT（最佳剂量为1000，次佳剂量为750或500），从移植前1天开始至移植后5天，每12 h给予受体胆红素。胆红素可改善糖尿病受者的血糖控制，提高糖耐量，降低血清中IL-1β、TNF-α、可溶性细胞间粘附分子1、单核细胞趋化蛋白1和NO水平，抑制枯否细胞向移植胰岛的浸润，恢复移植胰岛的胰岛素分泌能力。
Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1β, TNF-α and IFN-γ) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and protected the insulin secretory function of INS-1 cells. Diabetic inbred male Lewis rats induced by streptozotocin underwent IPIT at different islet equivalents (IEQs)(optimal dose of 1000, and suboptimal doses of 750 or 500), and bilirubin was administered to the recipients every 12 h, starting from one day before transplantation until 5 days after transplantation. Administration of bilirubin improved glucose control and enhanced glucose tolerance in diabetic recipients, and reduced the serum levels of inflammatory mediators including IL-1β, TNF-α, soluble intercellular adhesion molecule 1, monocyte chemoattractant protein-1 and NO, and inhibited the infiltration of Kupffer cells into the islet grafts, and restored insulin-producing ability of transplanted islets.
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影响因子：
4.7
作者：
Amoli, MM;Larijani, B
通讯作者：
Larijani, B
影响因子：
5
作者：
John T. Wilson;E. Chaikof
通讯作者：
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作者：
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DOI：
10.1161/01.atv.0000118279.74056.8a
发表时间：
2004-03-01
影响因子：
8.7
作者：
Lindenblatt, N;Bordel, R;Vollmar, B
通讯作者：
Vollmar, B
影响因子：
7.7
作者：
Contreras, JL;Eckstein, C;Eckhoff, DE
通讯作者：
Eckhoff, DE