Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury
Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury
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DOI：
10.1097/ta.0b013e31823c54a6
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发表时间：
2012-03-01
影响因子：
3.4
通讯作者：
Fu, Zhi-Jun
中科院分区：
文献类型：
--
作者：
Gao, Tie-Lei;Yuan, Xiang-Tian;Fu, Zhi-Jun
背景技术背景：越来越多的证据表明，炎症反应有助于继发性脑损伤，在创伤性脑损伤（TBI）患者的临床结局中起着关键作用。最近，高迁移率族蛋白1（HMGB 1）已被确定为炎症反应中的关键细胞因子，并可能代表TBI治疗的新靶点。方法：采用Western blot法检测大鼠脑损伤后不同时间点HMGB 1和晚期糖基化终产物受体（receptor for advanced glycation end products，RECEPTOR）的表达水平。结果：大鼠脑内HMGB 1在伤后6 h明显下降至基础水平以下，2d后逐渐恢复至基础水平，伤后6 h开始恢复至基础水平。TBI后6小时表达增加，1天后达到高峰，然后缓慢下降，但仍高于假损伤组，直到TBI后6天。在大鼠和人脑中，HMGB 1在TBI后的早期阶段要么消失，要么从细胞核易位到细胞质，然后在后期阶段定位到吞噬性小胶质细胞的细胞质。在大鼠和人脑中，TBI后挫伤区域周围的区域中的cDNA 3表达增加。结论：HMGB 1在脑外伤后早期和晚期均有表达。靶向HMGB 1信号转导可能是治疗TBI的一种有前途的治疗方法。（J Trauma. 2012; 72：643-649.版权所有（c）2012 Lippincott威廉姆斯& Wilkins）
BACKGROUND: Increasing evidence suggests that an inflammatory reaction contributes to the secondary brain injury that plays a critical role in the clinical outcome of patients with traumatic brain injury (TBI). Recently, high-mobility group box 1 (HMGB1) has been identified as a key cytokine in the inflammatory reaction and may represent a new target for the treatment of TBI. However, the expression of HMGB1 during this injury process has not yet been studied.METHODS: In this study, the levels of both HMGB1 and receptor for advanced glycation end products (RAGE) in the rat brain were analyzed by Western blot at different time points after TBI. Immunohistochemistry was also performed to examine the expression pattern of HMGB1 and RAGE in both the rat and the human brain after TBI.RESULTS: In the rat brain, HMGB1 levels significantly declined below the basal level at 6 hours after TBI and then gradually returned to the basal level 2 days later. RAGE expression increased 6 hours after TBI and reached its peak after 1 day; this level then slowly decreased but remained higher than the sham-injury group until 6 days after TBI. In both rat and human brains, HMGB1 either disappeared or was translocated from the nucleus to the cytoplasm at early stages after TBI and then was localized to the cytoplasm of phagocytic microglia at later stages. RAGE expression increased in the region surrounding the contused area after TBI in both rat and human brains. At later stages, RAGE was mainly expressed in microglia.CONCLUSION: HMGB1 is involved in both early and later stages after TBI. Targeting HMGB1 signaling may be a promising therapeutic approach for the treatment of TBI. (J Trauma. 2012; 72: 643-649. Copyright (c) 2012 by Lippincott Williams & Wilkins)