中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1288-1293.doi: 10.4103/1673-5374.301022

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

抑制LncRNA-5657表达可缓解脓毒症脑病大鼠大脑海马中的炎症反应

  

  • 出版日期:2021-07-15 发布日期:2021-01-07
  • 基金资助:

    中国国家自然科学项目(81660314, 82060345),江西省自然科学基金项目(20192BAB205057)

Reducing LncRNA-5657 expression inhibits the brain inflammatory reaction in septic rats

Yi-An Zhan1, Xin-Liang Qiu2, Xu-Zhen Wang1, Ning Zhao1, Ke-Jian Qian1, *   

  1. 1 Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China;  2 Department of Critical Care Medicine, Xingguo County People’s Hospital, Ganzhou, Jiangxi Province, China
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Ke-Jian Qian, PhD, kejianqian21@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81660314, 82060345, and Jiangxi Provincial Natural Science Foundation of China, No. 20192BAB205057 (both to YAZ).

摘要:

作者预实验发现LncRNA-5657可降低大鼠小胶质细胞的炎症反应中炎症因子的表达,但是其在脓毒症脑病中的作用尚不清楚。(1)实验首先通过盲肠结扎穿刺建立大鼠脓毒症脑病模型,海马注射LncRNA-5657 shRNA进行治疗。结果发现shLncRNA-5657转染可明显减轻大鼠海马中神经元变性和坏死程度,降低海马中水通道蛋白4、乙酰肝素酶和基质金属蛋白酶9的免疫阳性反应,以及海马中肿瘤坏死因子α水平;(2)以经shLncRNA-5657预处理24h的小胶质细胞,以1 μg/mL脂多糖刺激干预。结果发现shLncRNA-5657转染可降低LPS干预小胶质细胞中LncRNA5657的表达,同时减少肿瘤坏死因子α、白细胞介素1β和白细胞介素6 mRNA和蛋白的表达;(3)表明抑制LncRNA-5657表达可显著缓解脓毒症脑病的炎症反应,对其产生保护作用。实验于2017年经南昌大学第一附属医院伦理委员会批准,批准号2017-004。

https://orcid.org/0000-0002-0742-0409 (Ke-Jian Qian)

关键词:

脓毒症, 脑损伤, 脂多糖, 炎症, 小胶质细胞, 长链非编码RNA, 损伤, 修复

Abstract: Our preliminary study found that the long noncoding RNA (LncRNA)-5657 can reduce the expression of inflammatory factors during inflammatory reactions in rat glial cells. However, the role played by LncRNA-5657 during septic brain injury remains unclear. In the present study, rat models of septic encephalopathy were established by cecal ligation and puncture, and then the rats were treated with a hippocampal injection small hairpin RNA (shRNA) against LncRNA-5657 (sh-LnCRNA-5657). The sh-LncRNA-5657 treatment reduced the level of neuronal degeneration and necrosis in the rat hippocampus, reduced the immunoreactivities of aquaporin 4, heparanase, and metallopeptidase-9, and lowered the level of tumor necrosis factor-alpha. Glial cells were pre-treated with sh-LncRNA-5657 and then treated with 1 µg/mL lipopolysaccharide. Sh-LncRNA-5657 transfection decreased the expression of LncRNA-5657 in lipopolysaccharide-treated glial cells and decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1β, and interleukin-6. These findings suggested that LncRNA-5657 expression can significantly reduce the inflammatory reaction during septic encephalopathy and induce protective effects against this disease. This study was approved by the Institutional Ethics Committee at the First Affiliated Hospital of Nanchang University of China (approval No. 2017-004) in 2017. 

Key words: brain injury, glial cells, inflammation, injury, lipopolysaccharide, long noncoding RNA, repair, sepsis