Department of Orthopaedics, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Avenue, Nanjing, 210000, Jiangsu, China.
Department of Orthopaedics, The Second Hospital, University of South China, Hengyang, 421000, Hunan, China.
J Orthop Surg Res. 2023 Jan 30;18(1):74. doi: 10.1186/s13018-023-03565-3.
Necrostatin-1 (Nec-1) is an inhibitor of the receptor interacting protein (RIP)1 kinase, which acts as an inhibitor of necroptosis, a special form of necrosis. In the present study, the effect of Nec-1 on peripheral nerve injury (PNI) was investigated.
The PNI model was established by inducing sciatic nerve injury. Hematoxylin-eosin and immunofluorescence staining techniques were used to assess the extent of injury to nerve fibers and necrosis of Schwann cells (SCs). Western blotting was performed to detect the expression of necroptosis-related factors (RIP1 and RIP3). The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and the oxidative stress-related enzyme malondialdehyde (MDA) were determined to indicate the degree of inflammation and oxidative stress.
Nec-1 could decrease the degree of peripheral nerve lesions after PNI and protect SCs and axons by inhibiting necroptosis. Furthermore, Nec-1 could reduce necroptosis by inhibiting RIP1 and effectively reduce inflammation and reactive oxygen species production at the early stage of PNI.
Alleviation of necroptosis by Nec-1 may provide new insights into therapies for the early stages of peripheral nerve repair after PNI.
坏死因子抑制剂-1（Nec-1）是受体相互作用蛋白（RIP）1 激酶的抑制剂，可抑制坏死性凋亡，这是一种特殊的细胞坏死形式。本研究旨在探讨 Nec-1 对周围神经损伤（PNI）的影响。
通过诱导坐骨神经损伤建立 PNI 模型。采用苏木精-伊红和免疫荧光染色技术评估神经纤维损伤和施万细胞（SCs）坏死程度。采用 Western blot 检测坏死相关因子（RIP1 和 RIP3）的表达。测定肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6 和氧化应激相关酶丙二醛（MDA）的浓度，以表明炎症和氧化应激的程度。
Nec-1 可减轻 PNI 后周围神经病变的程度，通过抑制坏死性凋亡来保护 SCs 和轴突。此外，Nec-1 通过抑制 RIP1 减少坏死性凋亡，并有效降低 PNI 早期的炎症和活性氧物质的产生。
Nec-1 减轻坏死性凋亡可能为 PNI 后早期周围神经修复提供新的治疗思路。
