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烫伤后高迁移率族蛋白B1对树突状细胞分泌细胞因子的影响

ISSN号：1008-9691
期刊名称：《中国中西医结合急救杂志》
时间：0
分类：Q786[生物学—分子生物学] Q813.11[生物学—生物工程]
作者机构：[1]解放军总医院第一附属医院全军烧伤研究所,北京 100037
相关基金：基金项目;国家重点基础研究发展规划项目（2005CB522602）;国家自然科学基金资助项目（30672178）;国家杰出青年科学基金课题（30125020）

作者：张笑天[1], 姚咏明[1], 黄立峰[1], 于燕[1], 盛志勇[1]

关键词：烧伤, 高迁移率族蛋白B1, 树突状细胞, 肿瘤坏死因子-Α, 白细胞介素一12, burns, high mobility group box-1 protein, dendritic cell, tumor necrosis factor-α, interleukin-12

中文摘要：

目的观察烫伤后大鼠高迁移率族蛋白B1（HMGBl）对树突状细胞（DC）分泌肿瘤坏死因子-α（TNF-α）和白细胞介素-12（IL-12）的影响及意义。方法将104只大鼠随机分为正常对照组（n=8）、假烫伤组（n=32）、烫伤组（n=32）和丙酮酸乙酯（EP）干预组（n=32），后3组实验动物按观察时间再分为4个亚组，分别于烫伤后1、3、5和7d分别处死各组动物留取脾脏。分离DC后培养24h，收集孵育液，采用酶联免疫吸附试验检测TNF-α和IL-12水平；采用荧光定量聚合酶链反应（PCR）方法检测脾脏组织TNF-α、IL-12和HMGBl的基因表达。结果与相同时间点假烫伤组比较，伤后不同时间点烫伤组HMGBl mRNA表达显著升高（P均〈0．01），DC孵育液中TNF-α产生减少、IL-12的产生变化不明显，脾脏TNF-α mRNA于伤后1d显著升高，5～7d迅速降至假烫伤组水平，IL-12mRNA表达在伤后1d和3d显著下调，5d和7d则迅速增强（P〈0．05或P〈O．01）；与烫伤组比较，EP干预组HMGBl mRNA表达均明显受抑，脾脏DC分泌TNF-α和IL-12的能力以及脾脏IL-12mRNA表达均显著增强（P均〈O．01）。结论严重烫伤后HMGBl的表达异常升高，可导致脾脏DC分泌TNF-α和IL-12的能力下降，从而介导机体的免疫功能抑制。

英文摘要：

Objective To investigate the effects of high mobility group box-1 protein （HMGB1） on tumor necrosis factor-α （TNF-α） and interleukin-12 （IL-12） release of splenic dendritic cells （DCs） in rats after thermal injury. Methods One hundred and four rats were randomly divided into four groups as follows： normal control group （n=8）, sham burn group （n=32）, burn group （n= 32）, and burn with ethyl pyruvate （EP） treatment group （n~ 32）, and they were sacrificed on postburn days 1, 3, 5 and 7, respectively with 8 animals at each time point. MACS microbeads were used to isolate splenic DCs. Gene expressions of splenic TNF-α, IL-12 as well as HMGB1 were measured by real-time quantitative polymerase chain reaction （PCR） taken glyceraldehyde phosphate dehydrogenase （GAPDH） as the internal standard, and cytokine protein levels were determined with enzyme linked immunoadsorbent assay （ELISA） kits. Results Compared to sham burn group, the expression levels of splenic HMGB1 mRNA were significantly elevated during 1 - 7 days after burns （all P〈0.01）, TNF-α release from DCs was markedly decreased and IL-12 production was not significantly changed. Meanwhile, splenic TNF-α mRNA was significantly expressed on postburn day 1, while it recovered to sham burn value on 5 - 7 days. Splenic IL-12 mRNA expression was down-regulated on postburn days 1 and 3, but rapidly up-regulated on days 5 and 7 after injury （P〈0. 05 or P〈0.01）. Compared to burn group, however, administration of EP to inhibit HMGB1 mRNA could significantly enhance both TNF-α as well as IL-12 production and splenic IL-12 mRNA expression after burn injury （all P〈0.01）. Conclusion These data suggest that excessively released HMGB1 might induce dysfunction of splenic DCs and subsequent immunosuppression following severe burns.

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