中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (10): 2290-2298.doi: 10.4103/1673-5374.390958

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

枸杞糖肽可减缓N-甲基-N-亚硝基脲诱导光感受器的退化

  

  • 出版日期:2024-10-15 发布日期:2024-01-29
  • 基金资助:
    广州市脑科学与类脑智能技术重点项目(20200730009),国家自然科学基金项目(82074169);广东省基础与应用基础研究基金项目(2021A1515012473);广东省中医药管理局项目(20202045);爱尔眼科医院集团项目(AF2019001)

Lycium barbarum glycopeptide (wolfberry extract) slows N-methyl-N-nitrosourea-induced degradation of photoreceptors

Qihang Kong1, 2, #, Xiu Han3, #, Haiyang Cheng3, Jiayu Liu2, Huijun Zhang2, 4, Tangrong Dong5, Jiansu Chen1, 6, Kwok-Fai So3, 6, 7, 8, Xuesong Mi2, 6, *, Ying Xu3, 6, 7, *, Shibo Tang1, 6, *   

  1. 1Department of Ophthalmology, Aier Eye Hospital, Jinan University, Guangzhou, Guangdong Province, China; 2Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, China; 3Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, Guangzhou, Guangdong Province, China; 4Department of Ophthalmology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong Province, China; 5School of Stomatology, Jinan University, Guangzhou, Guangdong Province, China; 6Aier Academician Station, Changsha, Hunan Province, China; 7Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 8State Key Laboratory of Brain and Cognitive Sciences, Hong Kong  Special Administrative Region, China
  • Online:2024-10-15 Published:2024-01-29
  • Contact: Xuesong Mi, MD, PhD, mxsong@163.com; Ying Xu, PhD, xuying@jnu.edu.cn; Shibo Tang, MD, PhD, tangshibo@vip.163.com.
  • Supported by:
    This study was supported by Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology, No. 20200730009 (to YX), the National Natural Science Foundation of China, No. 82074169 (to XM); the Guangdong Basic and Applied Basic Research Foundation, No. 2021A1515012473 (to XM) and Project of Administration of Traditional Chinese Medicine of Guangdong Province, No. 20202045 (to XM); Aier Eye Hospital Group, No. AF2019001 (to ST, KFS, YX, and XM).

摘要:

光感受器退行性疾病可导致失明,且目前尚无有效的治疗方法。作者团队既往研究已发现,枸杞多糖可以保护色素性视网膜炎转基因模型rd1小鼠退化的光感受器。最近从枸杞多糖进一步分离提取出的枸杞糖肽,被认为是一种免疫反应性糖蛋白。为研究枸杞糖肽是否对化学诱导的光感受器退化有保护作用。实验首先对野生型小鼠以枸杞糖肽连续7d灌胃枸杞糖肽7天作为预保护,然后腹腔注射40mg/kg N-甲基-N-亚硝基脲诱导特异性光感受器损伤,再以枸杞糖肽治疗1周。结果证实,枸杞糖肽改善N-甲基-N-亚硝基脲诱导的光感受器变性小鼠的存活和光感受器结构,并进一步改善了视网膜光反应和视觉行为。进一步研究证实,枸杞糖肽可部分抑制N-甲基-N-亚硝基脲损伤视网膜中的小胶质细胞活化,降低一些促炎细胞因子的表达。因此,枸杞糖肽可能通过其抗炎作用有效减缓N-甲基-N-亚硝基脲损伤小鼠的光感受器变性,可能成为光感受器变性疾病临床治疗的候选药物。

https://orcid.org/0000-0001-9146-1715 (Xuesong Mi); https://orcid.org/0000-0002-9987-2057 (Ying Xu); https://orcid.org/0000-0003-2737-6780 (Shibo Tang)

关键词: 视紫红质, 视蛋白, 视网膜变性, 视网膜色素变性, 遗传性视网膜疾病, 光感受器, N-甲基-N-亚硝基脲, 枸杞糖肽, 抗炎, 反应性胶质增生

Abstract: Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum (L. barbarum) polysaccharide (LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide (LbGP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of LbGP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of LbGP as a protective pre-treatment on days 1–7; intraperitoneal administration of 40 mg/kg N-methyl-N-nitrosourea to induce photoreceptor injury on day 7; and continuation of orally administered LbGP on days 8–14. Treatment with LbGP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. LbGP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, LbGP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.

Key words: anti-inflammation, inherited retinal diseases, Lycium barbarum glycopeptide, N-methyl-N-nitrosourea, opsin, photoreceptor, reactive gliosis, retinal degeneration, retinitis pigmentosa, rhodopsin