Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice
Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice
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坏死性凋亡是一种新型的程序性细胞死亡，会导致成年小鼠脊髓损伤后的早期神经细胞损伤。
DOI：
10.1179/2045772314y.0000000224
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发表时间：
2015-11-01
影响因子：
1.7
通讯作者：
Hang, Chun-hua
中科院分区：
文献类型：
--
作者：
Liu, Ming;Wu, Wei;Hang, Chun-hua
背景：坏死性凋亡是传统坏死和细胞凋亡之外的一种新兴的程序性坏死。直到最近，还没有研究探讨坏死性凋亡与脊髓损伤（SCI）后细胞死亡发病机制之间的关系。目的：探讨坏死性凋亡是否参与小鼠创伤性SCI的早期病理生理过程。方法：将雌性ICR小鼠随机分为三组：假手术组、载体治疗+SCI组和Nec-1治疗+SCI组。为了诱导 SCI，小鼠在 T9 处接受椎板切除术并用血管夹压迫。 SCI 后 24 小时处死小鼠后，使用体内 PI 标记检测碘化丙啶 (PI) 阳性细胞。通过苏木精和伊红染色以及尼氏染色进行形态学分析。通过原位 TUNEL 测定评估样品的细胞凋亡。通过蛋白质印迹评估 caspase-3 的表达。损伤后1、3、5、7、14天采用BMS（Basso小鼠量表）评分评估后肢运动行为。结果：与二甲亚砜治疗组小鼠相比，necrostatin-1治疗组小鼠PI阳性细胞减少（P < 0.05），组织损伤减轻，SCI后24小时存活神经元增多（P < 0.05），改善第 7 天至第 14 天的功能恢复（P < 0.05）。 Necrostatin-1 不会降低 SCI 后 24 小时的 caspase-3 表达和 TUNEL 阳性细胞数量（P > 0.05）。结论：坏死性凋亡导致成年小鼠 SCI 后坏死性细胞死亡并影响功能结果。 necrostatin-1 对坏死性凋亡的抑制可能对 SCI 患者具有治疗潜力。
Background: Necroptosis is an emerging programmed necrosis other than traditional necrosis and apoptosis. Until recently, there have not been studies that have investigated a relationship between necroptosis and pathogenesis of cell death after spinal cord injury (SCI).Objective: To investigate whether necroptosis takes part in the early pathophysiological processes of traumatic SCI in mice.Methods: Female ICR mice were randomized equally into three groups: the sham, the vehicle-treated + SCI group, and the Nec-1-treated + SCI group. To induce SCI, the mice were subjected to a laminectomy at T9 and compression with a vascular clip. After mice were sacrificed 24 hours post-SCI, propidium iodide (PI)positive cells were detected using in vivo PI labeling. Morphological analyses were performed by hematoxylin and eosin staining and Nissl staining. The samples were evaluated for apoptosis by the in situ TUNEL assay. The expression of caspase-3 was assessed by western blot. Locomotor behavior of hindlimb was evaluated by BMS (Basso mouse scale) score at 1, 3, 5, 7, and 14 days post-injury.Results: Compared with dimethyl sulfoxide -treated mice, necrostatin-1-treated mice showed decreased PI-positive cells (P < 0.05), alleviated tissue damage, more surviving neuron at 24 hours after SCI (P < 0.05), and improved functional recovery from days 7 to 14 (P < 0.05). Necrostatin-1 did not reduce the expression of caspase-3 and the number of TUNEL-positive cells at 24 hours after SCI (P > 0.05).Conclusions: Necroptosis contributes to necroptotic cell death and influences functional outcome after SCI in adult mice. The inhibition of necroptosis by necrostatin-1 may have therapeutic potential for patients with SCI.