解放军医学杂志2011,Vol.36Issue(1):17-20,4.
高迁移率族蛋白B1对烫伤大鼠调节性T细胞表型及T细胞功能极化的影响
Effects of high mobility group box-1 (HMGB1) protein on phenotype of regulatory T cells and functional polarization of T cells in burned rots
摘要
Abstract
Objective To explore the effects of high mobility group box-1 (HMGB1) protein expression on the phenotype of regulatory T cells (Treg) and the functional polarization of splenic T cells in severe burn rata after delayed resuscitation. Methods One hundred and four Wistar rats were involved in present study and randomly divided into normal control group (n=8), sham bum group (n=32), bum group (n=32) and ethyl pyruvate (EP) treatment group (n=32). Thirty percent TBSA full-thickness bum models were established with the animals in both bum and EP treatment group, and Ringer's solution or EP solution was respectively injected intraperitoneally for delayed resuscitation Animals in each of the later three groups were further divided into four subgroups (8 each),sacrificed and simultaneously harvesting the spleen samples on day 1, 3, 5 and 7 after bum, respectively. Spleen CD4+ CD25+ Treg were isolated by magnetic-activated cell sorting (MACS) system. The levels of HMGB1 in splenic tissue and IL-4, IFN-γ in T cells supernatam were determined by ELISA, and the expression of forkhead/winged helix transcription factor 3 (Foxp3) as a surface marker of Treg was analyzed by flow cytometry. Results Compared with those in sham burn group, the HMGB1 levd elevated significantly at day 1 to 7 (P <0. 01), reached the peak value (46. 73±8. 27ng/mg) on day 1, and declined obviously (P<0. 01) by EP treatment in bum group; The expression of Foxp3 on splenic Treg increased from day 1 and reached the peak (72. 46%±11.02%) on day 3 in bum group, while after EP treatment, it decreased obviously on day 1 to 7 (P<0. 01 or 0. 05). The IL-4 level increased (P<0. 01 or 0. 05) and IFN-γ level decreased (P<0. 01) markedly in bum group compared with those in sham bum group. The IL-4 level was significantly lower (P<0. 05)on day 1 to 5, while the IFN-γ level was markedly higher on day 1 to 7 (P<0.05), in EP group than in bum group. Conclusion The excessive release of HMGB1 after severe bum might stimulate the maturation of splenic CD4+ CD25+ Treg, thereby mediate the transformation of T cell subsets from Thl to Th2 and induce the inhibition of cellular immunity.关键词
HMGB1蛋白/T淋巴细胞,调节性/叉头转录因子类/烧伤Key words
HMGB1 protein/ T-lymphocytes, regulatory/ forkhead transcription factors/ burns分类
医药卫生引用本文复制引用
黄立锋,姚凤华,董宁,张立天,姚咏明..高迁移率族蛋白B1对烫伤大鼠调节性T细胞表型及T细胞功能极化的影响[J].解放军医学杂志,2011,36(1):17-20,4.基金项目
国家自然科学基金(30872683,30901561) (30872683,30901561)
国家重点基础研究发展规划(2005CB522602) (2005CB522602)