Li Haotian, Zhang Xinran, Zhu Xu, Qi Xi, Lin Kaili, Cheng Liming
Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Tongji University, Shanghai, China.
Front Physiol. 2018 Nov 16;9:1617. doi: 10.3389/fphys.2018.01617. eCollection 2018.
Spinal cord injury (SCI) is a severe medical problem leading to crucial life change. Icariin (ICA) is a natural flavonoid compound extracted from the Chinese herb Epimedium brevicornum which has neuroprotective effects. But little is known about the relationship between ICA and SCI. We hypothesized ICA may enhance motor recovery through attenuating inflammation, oxidative stress and mitochondrial dysfunction. Mice were randomly assigned to sham, SCI, ICA 20 μmol/kg (low dose) and ICA 50 μmol/kg (high dose) groups. And Behavioral, biochemical, molecular biological, immunofluorescent and histological assays were performed. First, ICA enhanced motor recovery greatly at 14, 28, and 42 days and protected spinal cord tissues especially in the high dose group. Meanwhile, ICA decreased the production of interleukin-1 beta, tumor necrosis factor-alpha and inducible nitric oxide synthase at 24 h and 3 days after SCI. The level of mitochondrial reduced glutathione, superoxide dismutase, adenosine triphosphate (ATP), Na-K-ATPase, mitochondrial membrane potential, state III respiration rate and the respiratory control ratio were also significantly increased, while malondialdehyde level and Ca concentration were decreased by ICA. Furthermore, ICA decreased the expression of mitochondrial apoptotic proteins at 3 days after SCI. More importantly, transferase UTP nick end labeling (TUNEL) and Nissl staining implied that ICA at a high dose inhibited the neuronal apoptosis after SCI. Our research indicated that early and continuous treatment of ICA at a high dose significantly enhanced motor recovery after SCI through inhibiting pro-inflammatory factors, oxidative stress and neuronal apoptosis via mitochondrial apoptotic pathway.
脊髓损伤（SCI）是一个严重的医学问题，会导致生活发生重大改变。淫羊藿苷（ICA）是从中国草药淫羊藿中提取的一种具有神经保护作用的天然黄酮类化合物。但关于ICA与SCI之间的关系知之甚少。我们推测ICA可能通过减轻炎症、氧化应激和线粒体功能障碍来促进运动功能恢复。将小鼠随机分为假手术组、SCI组、ICA 20 μmol/kg（低剂量）组和ICA 50 μmol/kg（高剂量）组。并进行了行为学、生物化学、分子生物学、免疫荧光和组织学检测。首先，ICA在第14、28和42天极大地促进了运动功能恢复，并保护了脊髓组织，尤其是高剂量组。同时，ICA在SCI后24小时和3天时降低了白细胞介素-1β、肿瘤坏死因子-α和诱导型一氧化氮合酶的产生。线粒体还原型谷胱甘肽、超氧化物歧化酶、三磷酸腺苷（ATP）、钠钾-ATP酶、线粒体膜电位、状态III呼吸速率和呼吸控制率水平也显著升高，而丙二醛水平和钙浓度则被ICA降低。此外，ICA在SCI后3天时降低了线粒体凋亡蛋白的表达。更重要的是，末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）和尼氏染色表明高剂量的ICA抑制了SCI后的神经元凋亡。我们的研究表明，高剂量ICA的早期和持续治疗通过线粒体凋亡途径抑制促炎因子、氧化应激和神经元凋亡，显著促进了SCI后的运动功能恢复。
