脊髓损伤(SCI)是一种破坏性疾病,治疗选择很少。二甲双胍,一种经典的抗糖尿病和抗氧化剂,已将其应用扩展到实验性SCI治疗。这里,我们进行了系统评价,以评估二甲双胍治疗大鼠SCI的神经生物学作用,并评估临床翻译的潜力。PubMed,Embase,中国国家知识基础设施,万方数据,SinoMed,和VipJournal集成平台数据库从成立日期到2021年10月进行了搜索。两名评审员独立选择对照研究,评估二甲双胍在SCI后大鼠的神经生物学作用,提取数据,并评估方法和证据的质量。成对荟萃分析,采用亚组分析和网络分析评估二甲双胍在SCI大鼠神经功能和组织损伤中的作用.本系统综述包括12篇文章。大多数方法质量中等到高,而这些研究的证据质量不高。一般来说,巴索,Beattie,与对照组相比,二甲双胍治疗的大鼠的Bresnahan评分增加,二甲双胍组和对照组之间的加权平均差异(WMDs)从第3组开始呈逐渐上升的趋势(9项研究,n=164,WMD=0.42,95%CI=-0.01至0.85,P=0.06)至治疗后第28天(9项研究,n=136,WMD=3.48,95%CI=2.04~4.92,P<0.00001)。二甲双胍干预与斜面评分改善相关,组织保存率和前角运动神经元数量。亚组分析表明神经保护与二甲双胍剂量之间存在关联。网络荟萃分析显示,50mg/kg二甲双胍比10和100mg/kg二甲双胍表现出更大的保护作用。二甲双胍的作用机制与激活单磷酸腺苷激活的蛋白激酶信号有关,调节线粒体功能和缓解内质网应激。总的来说,本综述表明二甲双胍对SCI具有保护作用,且安全性良好,我们证实了其合理的作用机制;二甲双胍是未来临床试验的有希望的候选药物.然而,鉴于动物实验方法学和证据质量的局限性,本临床前综述的结果应谨慎解释.
Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to experimental SCI treatment. Here, we performed a systematic
review to evaluate the neurobiological roles of metformin for treating SCI in rats, and to assess the potential for clinical translation. PubMed, Embase, China National Knowledge Infrastructure, WanFang data, SinoMed, and Vip Journal Integration Platform databases were searched from their inception dates to October 2021. Two reviewers independently selected controlled studies evaluating the neurobiological roles of metformin in rats following SCI, extracted data, and assessed the quality of methodology and evidence. Pairwise meta-analyses, subgroup analyses and network analysis were performed to assess the roles of metformin in neurological function and tissue damage in SCI rats. Twelve articles were included in this systematic
review. Most of them were of moderate-to-high methodological quality, while the quality of evidence from those studies was not high. Generally, Basso, Beattie, and Bresnahan scores were increased in rats treated with metformin compared with controls, and the weighted mean differences (WMDs) between metformin and control groups exhibited a gradual upward trend from the 3rd (nine studies, n = 164, WMD = 0.42, 95% CI = -0.01 to 0.85, P = 0.06) to the 28th day after treatment (nine studies, n = 136, WMD = 3.48, 95% CI = 2.04 to 4.92, P < 0.00001). Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons. Subgroup analyses indicated an association between neuroprotection and metformin dose. Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin. The action mechanisms behind metformin were associated with activating adenosine monophosphate-activated protein kinase signaling, regulating mitochondrial function and relieving endoplasmic reticulum stress. Collectively, this
review indicates that metformin has a protective effect on SCI with satisfactory safety and we demonstrate a rational mechanism of action; therefore, metformin is a promising candidate for future clinical trials. However, given the limitations of animal experimental methodological and evidence quality, the findings of this pre-clinical
review should be interpreted with caution.