Afshari Khashayar, Dehdashtian Amir, Haddadi Nazgol-Sadat, Haj-Mirzaian Arvin, Iranmehr Arad, Ebrahimi Mohammad Ali, Tavangar Seyed Mohammad, Faghir-Ghanesefat Hedyeh, Mohammadi Fatemeh, Rahimi Nastaran, Javidan Abbas Norouzi, Dehpour Ahmad Reza
MD-MPH, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Spinal Cord. 2018 Nov;56(11):1032-1041. doi: 10.1038/s41393-018-0168-x. Epub 2018 Jun 29.
This is an animal study.
Metformin is a safe drug for controlling blood sugar in diabetes. It has been shown that metformin improves locomotor recovery after spinal cord injury (SCI). Neuropathic pain is also a disturbing component of SCI. It is indicated that metformin has neuroprotective and anti-inflammatory effects, which attenuate neuropathic pain and hyperalgesia in injured nerves. Thus, we evaluated metformin's therapeutic effects on SCI neuroinflammation and its sensory and locomotor complications. Meanwhile, results were compared to minocycline, an anti-neuroinflammation therapy in SCI.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Iran METHODS: In an animal model of SCI, 48 male rats were subjected to T9 vertebra laminectomy. Animals were divided into a SHAM-operated group and five treatment groups. The treatments included normal saline as a vehicle control group, minocycline 90 mg/kg and metformin at the doses of 10, 50 and 100 mg/kg. Locomotor scaling, behavioral tests for neuropathic pain and weight changes were evaluated and compared through a 28-days period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes.
Metformin 50 mg/kg improved the locomotors ability (p < 0.001) and decreased sensitivity to mechanical and thermal allodynia (p < 0.01). These results were compatible with minocycline effect on SCI (p > 0.05). While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-α and interleukin-1β (p < 0.001).
Metformin could be considered as an alternative therapeutic agent for SCI, as it potentially attenuates neuroinflammation, sensory and locomotor complications of cord injury.
这是一项动物研究。
二甲双胍是控制糖尿病血糖的一种安全药物。研究表明，二甲双胍可改善脊髓损伤（SCI）后的运动功能恢复。神经性疼痛也是SCI的一个困扰因素。有迹象表明，二甲双胍具有神经保护和抗炎作用，可减轻受损神经的神经性疼痛和痛觉过敏。因此，我们评估了二甲双胍对SCI神经炎症及其感觉和运动并发症的治疗效果。同时，将结果与米诺环素（一种用于SCI的抗神经炎症疗法）进行比较。
伊朗德黑兰医科大学实验医学研究中心
在SCI动物模型中，对48只雄性大鼠进行T9椎体椎板切除术。动物被分为假手术组和五个治疗组。治疗包括作为载体对照组的生理盐水、90mg/kg的米诺环素以及10、50和100mg/kg剂量的二甲双胍。在28天的时间内评估并比较运动评分、神经性疼痛行为测试和体重变化。研究结束时，采集组织样本以评估神经炎症变化。
50mg/kg的二甲双胍改善了运动能力（p<0.001），并降低了对机械性和热性异常性疼痛的敏感性（p<0.01）。这些结果与米诺环素对SCI的作用相当（p>0.05）。虽然二甲双胍导致体重减轻，但在脊髓组织组织病理学评估中，二甲双胍和米诺环素均显著降低了神经炎症以及肿瘤坏死因子-α和白细胞介素-1β的水平（p<0.001）。
二甲双胍可被视为SCI的替代治疗药物，因为它可能减轻脊髓损伤的神经炎症、感觉和运动并发症。
