右美托咪定预处理通过下调高迁移率族蛋白 B1- Toll 样受体 4-核因子 κB 信号通路减轻脊髓缺血再灌注损伤后的炎症和血脊髓屏障损伤。

Dexmedetomidine Preconditioning Ameliorates Inflammation and Blood-Spinal Cord Barrier Damage After Spinal Cord Ischemia-Reperfusion Injury by Down-Regulation High Mobility Group Box 1-Toll-Like Receptor 4-Nuclear Factor κB Signaling Pathway.

机构信息

Department of Anesthesiology, Liyuan Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Spine (Phila Pa 1976). 2019 Jan 15;44(2):E74-E81. doi: 10.1097/BRS.0000000000002772.

DOI:10.1097/BRS.0000000000002772

PMID:29975331

Abstract

STUDY DESIGN

To evaluate the effect of Dexmedetomidine (Dex) on the inflammatory response and the integrity of blood-spinal cord barrier (BSCB) after spinal cord ischemia-reperfusion injury (SCIRI).

OBJECTIVE

To investigate the role of Dex in spinal cord I/R, particularly in the high mobility group box 1-toll-like receptor 4-nuclear factor κB (HMGB1-TLR4-NF-κB) pathway and the integrity of BSCB.

SUMMARY OF BACKGROUND DATA

High mobility group box 1 (HMGB1) has been identified as a key mediator for the inflammatory response after spinal cord injury. Toll-like receptor 4-nuclear factor κB (TLR4-NF-κB) signaling pathway is the downstream of HMGB1. Dex preconditioning could protect the spinal cord from I/R injury by inhibiting HMGB1 and stabilizing the integrity of BSCB. But its underlying mechanism is not fully understood.

METHODS

Forty-eight male Japanese white rabbits were randomly assigned to three groups (16 rabbits/group): sham, I/R, and Dex + I/R. The hind-limb motor function was assessed at 12 hours intervals for 48 hours after reperfusion using the modified Tarlov scale score. The expression of HMGB1, TLR4, NF-κB, and tumor necrosis factor α (TNF-α) was evaluated by real-time polymerase chain reaction (RT-PCR) and Western blot. The permeability of BSCB was examined via Evans blue (EB) extravasation.

RESULTS

Compared with sham group, spinal cord I/R increased the expression of HMGB1, TLR4, NF-κB, and TNF-α as well as the permeability of BSCB (P < 0.05). Spinal cord I/R induced the decline of the score of hind-limb motor function (P < 0.01). Preconditioning with Dex attenuated the up-regulation of the express of HMGB1, TLR4, NF-κB, TNF-α, and stabilized the permeability of BSCB (P < 0.05). Dex preconditioning also improved the hiatopathological outcome and the motor function (P < 0.01).

CONCLUSION

Dex preconditioning may inhibit the inflammatory response and stabilize the integrity of BSCB at least partially by inhibiting the HMGB1-TLR4-NF-κB signaling pathway to protect spinal cord from ischemia/reperfusion injury.

LEVEL OF EVIDENCE

摘要

研究设计

评估右美托咪定（Dex）对脊髓缺血再灌注损伤（SCIRI）后炎症反应和血脊髓屏障（BSCB）完整性的影响。

目的

探讨 Dex 在脊髓 I/R 中的作用，特别是在高迁移率族蛋白 1- Toll 样受体 4-核因子 κB（HMGB1-TLR4-NF-κB）通路和 BSCB 完整性中的作用。

背景资料总结

高迁移率族蛋白 1（HMGB1）已被确定为脊髓损伤后炎症反应的关键介质。Toll 样受体 4-核因子 κB（TLR4-NF-κB）信号通路是 HMGB1 的下游。Dex 预处理可通过抑制 HMGB1 和稳定 BSCB 的完整性来保护脊髓免受 I/R 损伤。但其潜在机制尚不完全清楚。

方法

48 只雄性日本白兔随机分为三组（每组 16 只）：假手术组、I/R 组和 Dex+I/R 组。再灌注后 12 小时间隔 48 小时，采用改良 Tarlov 量表评分评估后肢运动功能。采用实时聚合酶链反应（RT-PCR）和 Western blot 法检测 HMGB1、TLR4、NF-κB 和肿瘤坏死因子 α（TNF-α）的表达。通过 Evans 蓝（EB）渗出检测 BSCB 的通透性。

结果

与假手术组相比，脊髓 I/R 增加了 HMGB1、TLR4、NF-κB 和 TNF-α的表达以及 BSCB 的通透性（P<0.05）。脊髓 I/R 导致后肢运动功能评分下降（P<0.01）。Dex 预处理可减轻 HMGB1、TLR4、NF-κB、TNF-α表达的上调，并稳定 BSCB 的通透性（P<0.05）。Dex 预处理还改善了组织病理学结果和运动功能（P<0.01）。