中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (7): 1535-1541.doi: 10.4103/1673-5374.358612

• 原著:退行性病与再生 • 上一篇    下一篇

大黄素减轻实验性自身免疫性脑脊髓炎的炎症和脱髓鞘反应

  

  • 出版日期:2023-07-15 发布日期:2023-01-12
  • 基金资助:
    国家自然科学基金项目(81771271);辽宁省重点研发计划项目(2020JH2/10300047);盛京医院杰出科学基金项目

Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis

Yue-Ran Cui, Zhong-Qi Bu, Hai-Yang Yu, Li-Li Yan, Juan Feng*   

  1. Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2023-07-15 Published:2023-01-12
  • Contact: Juan Feng, MD, PhD, juanfeng@cmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81771271; Key Research and Development Program of Liaoning Province, No. 2020JH2/10300047; and Outstanding Scientific Fund of Shengjing Hospital (all to JF).

摘要:

大黄素是一种从大黄等中草药的提取物,对中枢神经系统有神经保护作用,但其对多发性硬化的潜在治疗作用尚不清楚。实验通过免疫诱导建立实验性自身免疫性脑脊髓炎大鼠模型,模拟多发性硬化,并从免疫诱导日起腹腔注射大黄素(20 mg/kg/d)至处死。结果可见大黄素可明显改善实验性自身免疫性脑脊髓炎大鼠的体重减轻和神经障碍,减轻炎症细胞浸润和脱髓鞘程度,降低炎症细胞因子的表达,抑制小胶质细胞的聚集和活化,减少NLRP3信号相关分子的表达,增加SIRT1和过氧化物酶体增殖物激活受体γ共激活因子1α表达。提示大黄素可用于治疗实验性自身免疫性脑脊髓炎,且其作用与调节SIRT1/过氧化物酶体增殖物激活受体γ共激活因子1α/NLRP3信号通路以及抑制小胶质细胞炎症水平有关。这一研究为临床应用大黄素治疗多发性硬化提供了实验依据,并丰富了大黄素的临床应用范围。

https://orcid.org/0000-0002-1815-7036 (Juan Feng)

关键词: 大黄素, 实验性自身免疫性脑脊髓炎, 多发性硬化, 神经炎症, 脱髓鞘, NLRP3炎症小体, 细胞焦亡, 小胶质细胞, SIRT1, 过氧化物酶体增殖物激活受体γ共激活因子1α

Abstract: Emodin, a substance extracted from herbs such as rhubarb, has a protective effect on the central nervous system. However, the potential therapeutic effect of emodin in the context of multiple sclerosis remains unknown. In this study, a rat model of experimental autoimmune encephalomyelitis was established by immune induction to simulate multiple sclerosis, and the rats were intraperitoneally injected with emodin (20 mg/kg/d) from the day of immune induction until they were sacrificed. In this model, the nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and the microglia exacerbated neuroinflammation, playing an important role in the development of multiple sclerosis. In addition, silent information regulator of transcription 1 (SIRT1)/peroxisome proliferator-activated receptor-alpha coactivator (PGC-1α) was found to inhibit activation of the NLRP3 inflammasome, and SIRT1 activation reduced disease severity in experimental autoimmune encephalomyelitis. Furthermore, treatment with emodin decreased body weight loss and neurobehavioral deficits, alleviated inflammatory cell infiltration and demyelination, reduced the expression of inflammatory cytokines, inhibited microglial aggregation and activation, decreased the levels of NLRP3 signaling pathway molecules, and increased the expression of SIRT1 and PGC-1α. These findings suggest that emodin improves the symptoms of experimental autoimmune encephalomyelitis, possibly through regulating the SIRT1/PGC-1α/NLRP3 signaling pathway and inhibiting microglial inflammation. These findings provide experimental evidence for treatment of multiple sclerosis with emodin, enlarging the scope of clinical application for emodin. 

Key words: demyelination, emodin, experimental autoimmune encephalomyelitis, microglia, multiple sclerosis, neuroinflammation, NLRP3 inflammasome, PGC-1α, pyroptosis, SIRT1