基础医学与临床 ›› 2022, Vol. 42 ›› Issue (1): 94-99.doi: 10.16352/j.issn.1001-6325.2022.01.014

• 研究论文 • 上一篇    下一篇

特异性坏死性凋亡抑制剂-1(Nec-1)减轻脊髓损伤模型大鼠胶质瘢痕的形成

陈胜, 王春明, 严雪飞, 毛渊青*   

  1. 南京医科大学附属江苏盛泽医院/南京医科大学康达学院盛泽临床医学院 骨科, 江苏 苏州 215228
  • 收稿日期:2020-11-09 修回日期:2021-05-10 出版日期:2022-01-05 发布日期:2022-01-05
  • 通讯作者: * bendan841108@vip.qq.com
  • 基金资助:
    南京医科大学江苏康达医药卫生发展研究院科研项目(2017NJMUKD005);苏州市医学重点学科项目(SZXK201824);苏州市科技局民生科技关键技术应用研究(SS201850);吴江区卫计委“科教兴国”项目(WWK201820)

Specific necroptosis inhibitor-1(Nec-1) attenuates glial scar formation in rat models with spinal cord injury

CHEN Sheng, WANG Chun-ming, YAN Xue-fei, MAO Yuan-qing*   

  1. Department of Orthopaedics,the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University/Shengze Clinical Medical School, Kangda College of Nanjing Medical University, Suzhou 215228, China
  • Received:2020-11-09 Revised:2021-05-10 Online:2022-01-05 Published:2022-01-05
  • Contact: * bendan841108@vip.qq.com

摘要: 目的 观察特异性坏死性凋亡抑制剂-1(Nec-1)对脊髓损伤模型大鼠胶质瘢痕形成的影响及其机制。方法 将大鼠随机分为假手术组、模型组(坠落法)及受体相互作用蛋白激酶1(RIPK1)抑制剂Nec-1组(在大鼠侧脑室注射10 μmol/L Nec-1 10 μL)。BBB评分法测定大鼠后肢运动功能,免疫荧光检测胶质瘢痕形成,Western blot检测组织蛋白酶(cathepsin)B、caspase-3、胶质纤维酸性蛋白(GFAP)和vimentin表达。结果 术后第14天,与假手术组相比,模型组和Nec-1组BBB评分值均显著降低(P<0.05),与模型组相比,Nec-1组BBB评分值显著升高(P<0.05)。术后第14天,假手术组未见NF-200荧光,模型组及Nec-1组均可见NF-200荧光,与模型组相比,Nec-1组NF-200荧光标记强度显著降低(P<0.05)。术后第7天及14天,与假手术组相比,模型组、Nec-1组cathepsin B、caspase-3、GFAP、vimentin蛋白水平显著升高(P<0.05),与模型组相比,Nec-1组cathepsin B、caspase-3、GFAP和vimentin蛋白水平显著降低(P<0.05)。结论 Nec-1可能通过调控cathepsinB和caspase表达,减轻大鼠脊髓损伤后胶质瘢痕形成,促进神经功能恢复。

关键词: 脊髓损伤, 胶质瘢痕, 坏死性凋亡抑制剂-1(Nec-1), cathepsin B

Abstract: Objective To observe the effect of necroptosis inhibitor-1(Nec-1) on glial scar formation in rats with spinal cord injury and its mechanism. Methods The rats were randomly divided into sham group, model group (falling method) and RIPK1 inhibitor Nec-1 group (10 μmol/L Nec-1 10μL was injected into lateral ventricle). BBB method was used to measure the motor function of hind limbs, immunofluorescence was used to detect the formation of glial scar, and Western blot was used to detect the expression of cathepsin B, caspase-3, GFAP and vimentin. Results On the 14th day after operation, compared with the sham group, the BBB scores of the model group and Nec-1 group were significantly lower (P<0.05), compared with the model group, the BBB score of Nec-1 group was significantly higher (P<0.05). NF-200 fluorescence was not found in the sham operation group, but in the model group and Nec-1 group, the intensity of NF-200 fluorescence labeling in Nec-1 group decreased significantly(P<0.05). On the 7th and 14th day after operation, compared with the sham operation group, the protein level of cathepsin B, caspase-3, GFAP and vimentin in the model group and Nec-1 group was significantly higher(P<0.05),while the protein level of cathepsin B, caspase-3, GFAP and vimentin in Nec-1 group decreased significantly (P<0.05). Conclusions Nec-1 may regulate expression level of cathepsin B and caspase-3, reduce the expression of GFAP and vimentin proteins, reduce the formation of glial scar after spinal cord injury and promote the recovery of neural function.

Key words: spinal cord injury, glial scar, necroptosis inhibitor-1(Nec-1), cathepsin B

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