中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 2109-2120.doi: 10.4103/1673-5374.303537

• 原著:视神经损伤修复保护与再生 • 上一篇    

木犀草素减缓遗传性视网膜色素变性小鼠视网膜感光细胞的变性

  

  • 出版日期:2021-10-15 发布日期:2021-03-19
  • 基金资助:

    中国国家自然科学基金项目（81470656，82071372，82074169）；广东省脑部疾病关键技术研究项目（2018B030332001）；宁夏自回族治区重点研究与发展计划；中国大学引进学科人才计划（B14036）；生物实验室杰出学者计划（广州市再生医学与健康省级实验室）（2018GZR110102002）；广州科学技术计划（202007030012）

Luteolin delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

Xiao-Bin Liu1, Feng Liu1, Yi-Yao Liang1, Gang Yin2, Hui-Jun Zhang3, Xue-Song Mi3, Zai-Jun Zhang2, Kwok-Fai So1, 4, 5, Ang Li1, 4, *, Ying Xu1, 5, *#br#   

  1. 1Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China; 2Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University, Guangzhou, Guangdong Province, China; 3Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; 4Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 5Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Ying Xu, PhD, xuying@jnu.edu.cn; Ang Li, PhD, anglijnu@jnu.edu.cn.
  • Supported by:
    The work was supported by the National Natural Science Foundation of China, Nos. 81470656 (to YX), 82071372 (to AL), 82074169 (to XSM); Guangdong Grant Key Technologies for Treatment of Brain Disorders’, China, No. 2018B030332001 (to YX); Ningxia Key Research and Development Program Grant (Yinchuan, Ningxia Hui Autonomous Region, China) (to KFS); Program of Introducing Talents of Discipline to Universities, China, No. B14036 (to YX, AL, KFS); Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), No. 2018GZR110102002 (to KFS, AL); and Science and Technology Program of Guangzhou, No. 202007030012 (to KFS and AL).

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摘要：

既往研究显示，木犀草素对氧化损伤的视网膜神经节细胞和视网膜色素上皮细胞有神经保护作用，且可抑制小胶质细胞的神经毒性损伤，因而具有治疗视网膜疾病的潜力。实验以一种缓慢的视网膜色素变性感光受体变性模型转基因小鼠（rd10小鼠）为对象，拟探索木犀草素是否对其视杆细胞有保护作用。（1）rd10小鼠出生后14-25d时腹腔注射木犀草素（100 mg/kg），见木犀草素明显改善了rd10小鼠视觉表现和视网膜光反应，且还能提高感光细胞的存活率，缓解了视网膜结构的变化；（2）木犀草素能减轻活性氧生成，感光细胞凋亡，抑制反应性神经胶质增生，增加抗炎细胞因子的mRNA水平，同时降低促炎和趋化因子的mRNA水平，以及降低磷酸化JNK/JNK比值；（3）给予rd10小鼠腹腔注射JNK抑制剂SP600125产生与木犀草素相似的保护作用，提示木犀草素可能通过抑制JNK通路调节rd10小鼠视网膜氧化和炎症反应，从而延缓其光感受器变性和视神经功能的退化，可能成为视网膜色素变性的辅助药物。实验于2018年7月17日经暨南大学动物伦理委员会批准（批准号IACUC-20181217-02）。

https://orcid.org/0000-0002-9987-2057 (Ying Xu); https://orcid.org/0000-0002-9886-4880 (Ang Li)

关键词:

视网膜变性, 感光体, 视网膜色素变性, 类黄酮, 木犀草素, 抗炎, 细胞凋亡, JNK通路, 活性氧, 反应性胶质增生

Abstract: Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury, whereby it can inhibit microglial neurotoxicity. Therefore, luteolin holds the potential to be useful for treatment of retinal diseases. The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice, a slow photoreceptor-degenerative model of retinitis pigmentosa. Luteolin (100 mg/kg) intraperitoneally injected daily from postnatal day 14 (P14) to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25. Moreover, it increased the survival of photoreceptors and improved retinal structure. Mechanistically, luteolin treatment attenuated increases in reactive oxygen species, photoreceptor apoptosis, and reactive gliosis; increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines; and lowered the ratio of phospho-JNK/JNK. Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin, suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway. Therefore, luteolin may be useful as a supplementary treatment for retinitis pigmentosa. This study was approved by the Qualified Ethics Committee of Jinan University, China (approval No. IACUC-20181217-02) on December 17, 2018.

Key words: anti-inflammation, apoptosis, flavonoid, JNK pathway, luteolin, photoreceptor, reactive gliosis, reactive oxygen species, retinal degeneration, retinitis pigmentosa

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