HMGB1靶向治疗对创伤性脊髓损伤大鼠和小鼠的治疗效果及长期预后：一项系统评价和荟萃分析

Therapeutic effects and long-term outcomes of HMGB1-targeted therapy in rats and mice with traumatic spinal cord injury: A systematic review and meta-analysis.

作者信息

Deng Chen, Deng Li, Lv Junqiao, Sun Lin

机构信息

Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Tongji Shanxi Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China.

出版信息

Front Neurosci. 2022 Sep 7;16:968791. doi: 10.3389/fnins.2022.968791. eCollection 2022.

DOI:10.3389/fnins.2022.968791

PMID:36161176

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9489835/

Abstract

BACKGROUND

To date, the clinical need for therapeutic methods to prevent traumatic spinal cord injury (TSCI) progression and improve functional recovery has not been met. High mobility group box-1 (HMGB1) is released by necrotic neurons or secreted by glial cells after TSCI and plays an important role in pathophysiology.

OBJECTIVE

The purpose of this study was to evaluate the effects of HMGB1-targeted therapy on locomotor function recovery, inflammation reduction, edema attenuation, and apoptosis reduction in rat and mouse models of TSCI.

METHODS

We reviewed the literature on HMGB1-targeted therapy in the treatment and prognosis of TSCI. Twelve articles were identified and analyzed from four online databases (PubMed, Web of Science, Cochrane Library and Embase) based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and strict inclusion criteria.

RESULTS

The methodological quality of the 12 articles was poor. The results of the meta-analysis showed that compared with the SCI group, the treatment group had significantly increased locomotor function scores after SCI [ = 159, standardized mean difference (SMD) = 2.31, 95% confidence interval (CI) (1.52, 3.10), < 0.00001], and the change in locomotor function scores was significantly increased in both the drug and anti-HMGB1 Ab groups ( < 0.000001 and < 0.000001). A subgroup analysis showed significant differences ( > 0.05) between the drug group [(SMD) = 1.95, 95% CI (0.95, 2.94), = 0.0001] and the anti-HMGB1 Ab group [(SMD) = 2.89, 95% CI (1.66, 4.13), < 0.00001]. Compared with the SCI group, HMGB1 expression was significantly diminished [ = 76, SMD = -2.31, 95% CI (-3.71, -0.91), = 0.001], TNF-α levels were significantly reduced [ = 76, SMD = -2.52, 95% CI (-3.77, -1.27), < 0.0001], water content was significantly reduced [ = 44, SMD = -3.94, 95% CI (-6.28, -1.61), = 0.0009], and the number of apoptotic cells was significantly diminished [ = 36, SMD = -3.31, 95% CI (-6.40, -0.22), = 0.04] in the spinal cord of the treatment group.

CONCLUSION

HMGB1-targeted therapy improves locomotor function, reduces inflammation, attenuates edema, and reduces apoptosis in rats and mice with TSCI. Intrathecal injection of anti-HMGB1 Ab 0-3 h after SCI may be the most efficacious treatment.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO, identifier: CRD42022326114.

摘要

背景

迄今为止，预防创伤性脊髓损伤（TSCI）进展并改善功能恢复的治疗方法的临床需求尚未得到满足。高迁移率族蛋白B1（HMGB1）在TSCI后由坏死神经元释放或由神经胶质细胞分泌，在病理生理学中起重要作用。

目的

本研究旨在评估HMGB1靶向治疗对TSCI大鼠和小鼠模型运动功能恢复、炎症减轻、水肿消退和细胞凋亡减少的影响。

方法

我们回顾了关于HMGB1靶向治疗在TSCI治疗和预后方面的文献。根据系统评价和Meta分析的首选报告项目（PRISMA）指南和严格的纳入标准，从四个在线数据库（PubMed、Web of Science、Cochrane图书馆和Embase）中确定并分析了12篇文章。

结果

这12篇文章的方法学质量较差。Meta分析结果显示，与脊髓损伤（SCI）组相比，治疗组SCI后的运动功能评分显著提高[ = 159，标准化均数差（SMD）= 2.31，95%置信区间（CI）（1.52，3.10）， < 0.00001]，药物组和抗HMGB1抗体组的运动功能评分变化均显著增加（ < 0.000001和 < 0.000001）。亚组分析显示，药物组[（SMD）= 1.95，95% CI（0.95，2.94）， = 0.0001]和抗HMGB1抗体组[（SMD）= 2.89，95% CI（1.66，4.13）， < 0.00001]之间存在显著差异（ > 0.05）。与SCI组相比，治疗组脊髓中HMGB1表达显著降低[ = 76，SMD = -2.31，95% CI（-3.71，-0.91）， = 0.001]，肿瘤坏死因子-α水平显著降低[ = 76，SMD = -2.52，95% CI（-3.77，-1.27）， < 0.0001]，含水量显著降低[ = 44，SMD = -3.94，95% CI（-6.28，-1.61）， = 0.0009]，凋亡细胞数量显著减少[ = 36，SMD = -3.31，95% CI（-6.40，-0.22）， = 0.04]。