雷帕霉素在创伤性脑损伤动物模型中的治疗；一项系统评价和荟萃分析。
Treatment with Rapamycin in Animal Models of Traumatic Brain Injuries; a Systematic Review and Meta-Analysis.
作者信息
Kiah Mohammad, Azimi Amir, Hajisoltani Razieh, Yousefifard Mahmoud
机构信息
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Arch Acad Emerg Med. 2023 Dec 18;12(1):e16. doi: 10.22037/aaem.v12i1.2150. eCollection 2024.
INTRODUCTION
In light of the potential of enhanced functional and neurological recovery in traumatic brain injury (TBI) with the administration of rapamycin, this systematic review and meta-analysis aimed to investigate the efficacy of rapamycin treatment in animal models of TBI.
METHODS
An extensive search was conducted in the electronic databases of Medline, Embase, Scopus, and Web of Science by July 1, 2023. Two independent researchers performed the screening process by reviewing the titles and abstracts and the full texts of the relevant articles, including those meeting the inclusion criteria. Apoptosis rate, inflammation, locomotion, and neurological status were assessed as outcomes. A standardized mean difference (SMD) with a 95% confidence interval (95%CI) was calculated for each experiment, and a pooled effect size was reported. Statistical analyses were performed using STATA 17.0 software.
RESULTS
Twelve articles were deemed eligible for inclusion in this meta-analysis. Pooled data analysis indicated notable reductions in the number of apoptotic cells (SMD = -1.60; 95%CI: -2.21, -0.99, p<0.001), p-mTOR (SMD=-1.41; 95%CI: -2.03, -0.80, p<0.001), and p-S6 (SMD=-2.27; 95%CI: -3.03, -1.50, p<0.001) in TBI post-treatment. Our analysis also indicated substantial IL-1β reductions after rapamycin administration (SMD= -1.91; 95%CI: -2.61, -1.21, p<0.001). Moreover, pooled data analysis found significant neurological severity score (NSS) improvements at 24 hours (SMD= -1.16; 95%CI: -1.69, -0.62, p<0.001; I²=0.00%), 72 hours (SMD= -1.44; 95%CI: -2.00, -0.88, p<0.001; I²=0.00%), and 168 hours post-TBI (SMD= -1.56; 95%CI: -2.44, -0.68, p<0.001; I²=63.37%). No such improvement was observed in the grip test.
CONCLUSION
Low to moderate-level evidence demonstrated a significant decrease in apoptotic and inflammatory markers and improved neurological status in rodents with TBI. However, no such improvements were observed in locomotion recovery.
引言
鉴于雷帕霉素给药可能促进创伤性脑损伤（TBI）后的功能和神经恢复，本系统评价和荟萃分析旨在研究雷帕霉素治疗在TBI动物模型中的疗效。
方法
截至2023年7月1日，在Medline、Embase、Scopus和Web of Science电子数据库中进行了广泛检索。两名独立研究人员通过审查相关文章的标题、摘要和全文（包括符合纳入标准的文章）来进行筛选过程。将细胞凋亡率、炎症、运动能力和神经状态作为结局指标进行评估。为每个实验计算标准化均数差（SMD）及95%置信区间（95%CI），并报告合并效应量。使用STATA 17.0软件进行统计分析。
结果
12篇文章被认为符合纳入本荟萃分析的条件。汇总数据分析表明，TBI治疗后凋亡细胞数量（SMD = -1.60；95%CI：-2.21，-0.99，p<0.001）、磷酸化mTOR（p-mTOR，SMD=-1.41；95%CI：-2.03，-0.80，p<0.001）和磷酸化S6（p-S6，SMD=-2.27；95%CI：-3.03，-1.50，p<0.001）显著减少。我们的分析还表明，给予雷帕霉素后白细胞介素-1β（IL-1β）大幅降低（SMD= -1.91；95%CI：-2.61，-1.21，p<0.001）。此外，汇总数据分析发现，在TBI后24小时（SMD= -1.16；95%CI：-1.69，-0.62，p<0.001；I²=0.00%）、72小时（SMD= -1.44；95%CI：-2.00，-0.88，p<0.001；I²=0.00%）和168小时（SMD= -1.56；95%CI：-2.44，-0.68，p<0.001；I²=63.37%）时，神经严重程度评分（NSS）有显著改善。在握力测试中未观察到此类改善。
结论
低至中等水平的证据表明，TBI啮齿动物的凋亡和炎症标志物显著减少，神经状态得到改善。然而，在运动恢复方面未观察到此类改善。
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