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HMGB1作为脊髓损伤的治疗靶点:一种新型治疗方法开发的假说

HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development.

作者信息

Kikuchi Kiyoshi, Uchikado Hisaaki, Miura Naoki, Morimoto Yoko, Ito Takashi, Tancharoen Salunya, Miyata Kei, Sakamoto Rokudai, Kikuchi Chiemi, Iida Narumi, Shiomi Naoto, Kuramoto Terukazu, Miyagi Naohisa, Kawahara Ko-Ichi

机构信息

Department of Neurosurgery, Yame Public General Hospital, Yame 834-0034;

出版信息

Exp Ther Med. 2011 Sep;2(5):767-770. doi: 10.3892/etm.2011.310. Epub 2011 Jun 30.

Abstract

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

摘要

从历史上看,脊髓损伤(SCI)后的临床结果一直很不理想。严重的脊髓损伤会导致毁灭性的神经功能缺损,而且目前没有任何治疗方法能够将损伤导致的功能丧失恢复到足以保证独立生活的程度。要解决与脊髓损伤相关的所有问题,需要采用多学科方法,因为单一方法,如手术干预、药物治疗或细胞移植,不太可能足够有效。高迁移率族蛋白B1(HMGB1)是一种炎症细胞因子。各种研究表明,HMGB1在脊髓损伤中起关键作用,抑制HMGB1的释放可能是脊髓损伤的一种新型治疗靶点,可能有助于脊髓修复。此外,HMGB1与早期移植物排斥反应有关。因此,HMGB1可能是脊髓损伤移植患者有前景的治疗靶点。我们假设抑制HMGB1的释放可以挽救脊髓损伤患者。综上所述,我们的研究结果表明,抗HMGB1单克隆抗体或短发夹RNA介导的HMGB1可用于脊髓损伤患者的脊髓修复。

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