高迁移率族蛋白 B1 在脊髓损伤后上调，并与神经元细胞凋亡有关。

High mobility group box 1 is upregulated after spinal cord injury and is associated with neuronal cell apoptosis.

机构信息

Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.

出版信息

Spine (Phila Pa 1976). 2010 May 15;35(11):1109-15. doi: 10.1097/BRS.0b013e3181bd14b6.

DOI:10.1097/BRS.0b013e3181bd14b6

PMID:20195207

Abstract

STUDY DESIGN

Cerebrocortical culture and rat spinal cord injury (SCI) model were used to examine the expression of high mobility group box 1 (HMGB1), TNF-alpha, and Rage by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical examination. In addition, relationship between upregulation of HMGB1 and neural cells apoptosis was evaluated after SCI.

OBJECTIVE

To evaluate the upregulation of HMGB1, TNF-alpha, and Rage after SCI.

SUMMARY OF BACKGROUND DATA

It is known that the mode of delayed neuronal cell death after SCI is apoptosis. Apoptotic cell death is influenced by several injury-promoting factors which include pro-inflammatory cytokines. Inhibition of apoptosis promotes neurologic improvement following SCI. However, the factors which transmit inflammatory signaling following SCI have not yet been clarified in detail. HMGB1 was reported as an important mediator of inflammation. We examined the expression of HMGB1, TNF-alpha and Rage following acute SCI.

METHODS

Expression of HMGB1, TNF-alpha and Rage was examined by RT-PCR and immunohistochemical examination. Apoptotic cell death was evaluated by TUNEL methods.

RESULTS

HMGB1 was exported from nuclei to cytoplasm in active caspase-3 positive apoptotic cell in vitro. In addition, HMGB1, TNF-alpha, and Rage was expressed in same cell after NMDA treatment. RT-PCR revealed that expression of HMGB1 and TNF-alpha was upregulated following SCI. Immunohistochemical examination revealed that the numbers of HMGB1-, TNF-alpha-, and Rage-positive cells were increased following SCI. The number of TUNEL-positive cells was significantly increased at 12 hours after injury, and was maximal at 72 hours after injury. However, HMGB1- and TNF-alpha-positive cells were maximal in number 48 hours after injury, while Rage-positive cells were maximal in number at 24 hours after injury. These data suggest that HMGB1, TNF-alpha, and Rage were upregulated following SCI but preceding the apoptotic cell death.

CONCLUSION

Our findings suggest that HMGB1 play a role in the induction of apoptosis via inflammatory reaction.

摘要

研究设计

采用大脑皮质培养和大鼠脊髓损伤（SCI）模型，通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学检测，观察高迁移率族蛋白 1（HMGB1）、TNF-α和 Rage 的表达。此外，还评估了 SCI 后 HMGB1 上调与神经细胞凋亡的关系。

目的

评估 SCI 后 HMGB1、TNF-α和 Rage 的上调。

背景资料概要

已知 SCI 后神经元细胞延迟性死亡的方式为细胞凋亡。凋亡细胞的死亡受几种促炎因子的影响，包括促炎细胞因子。抑制细胞凋亡可促进 SCI 后的神经功能改善。然而，SCI 后传递炎症信号的因素尚未得到详细阐明。HMGB1 被报道为炎症的重要介质。我们检测了急性 SCI 后 HMGB1、TNF-α和 Rage 的表达。

方法

通过 RT-PCR 和免疫组织化学检测，检测 HMGB1、TNF-α和 Rage 的表达。通过 TUNEL 方法评估凋亡细胞死亡。

结果

HMGB1 在体外活性 caspase-3 阳性凋亡细胞中从核内转移到细胞质。此外，NMDA 处理后，HMGB1、TNF-α和 Rage 均在同一细胞中表达。RT-PCR 显示，SCI 后 HMGB1 和 TNF-α的表达上调。免疫组织化学检测显示，SCI 后 HMGB1、TNF-α和 Rage 阳性细胞数量增加。损伤后 12 小时 TUNEL 阳性细胞数量显著增加，72 小时达到高峰。然而，HMGB1 和 TNF-α阳性细胞数量在损伤后 48 小时达到高峰，而 Rage 阳性细胞数量在损伤后 24 小时达到高峰。这些数据表明，HMGB1、TNF-α和 Rage 在 SCI 后上调，但先于细胞凋亡。