中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1344-1350.doi: 10.4103/1673-5374.301027

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

槲皮素诱导血红素加氧酶1表达抑制糖尿病性视网膜病变

  

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

    国家自然科学基金项目(8120071881570866

Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression

Guang-Rui Chai1, Shu Liu2, Hong-Wei Yang1, Xiao-Long Chen1, *   

  1. 1 Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China;  2 Department of Geratology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Xiao-Long Chen, PhD, chenxl@sj-hospital.org.
  • Supported by:
    This study was sponsored by the National Natural Science Foundation of China, Nos. 81200718 (to HWY) and 81570866 (to XLC).

摘要:

槲皮素是一种常见的类黄酮,具有在抗癌、改善记忆力和心血管疾病的功能,但其对糖尿病性视网膜病是否有治疗作用尚有待研究。实验通过链脲佐菌素诱导建立糖尿病性视网膜病大鼠模型,造模后72h,连续16周腹腔注射槲皮素150 mg/kg。结果发现槲皮素可明显增加高血糖引起视网膜细胞层厚度,增加视网膜神经节细胞数量,降低视网膜组织中促炎因子白细胞介素1β、白细胞介素18、白细胞介素6和肿瘤坏死因子α的过表达,以及视网膜中高迁移率族蛋白B1过表达和NLRP3炎性小体过度激活,并抑制TLR4NF-κBp65的过表达,并促进促血管生成的血管内皮生长因子和可溶性细胞间黏附分子1以及神经营养相关的脑源性神经营养因子和神经生长因子的表达。而腹腔注射血红素加氧酶1抑制剂Znpp则逆转槲皮素的保护作用。表明槲皮素对糖尿病性视网膜病具有治疗作用,其作用可能与诱导血红素加氧酶1表达有关。实验于201648日经中国医科大学伦理委员会批准,批准号2016PS229K

https://orcid.org/0000-0001-7653-7515 (Xiao-Long Chen) 

关键词: 糖尿病性视网膜病变, 槲皮素, 血红素加氧酶1, 炎症, 血管生成, 神经营养, 类黄酮, 修复

Abstract: Quercetin is a widely-occurring flavonoid that protects against cancer, and improves memory and cardiovascular functions. However, whether quercetin exhibits therapeutic effects in diabetic retinopathy remains unclear. In this study, we established a rat model of streptozocin-induced diabetic retinopathy. Seventy-two hours later, the rats were intraperitoneally administered 150 mg/kg quercetin for 16 successive weeks. Quercetin markedly increased the thickness of the retinal cell layer, increased the number of ganglion cells, and decreased the overexpression of the pro-inflammatory factors interleukin-1β, interleukin-18, interleukin-6 and tumor necrosis factor-α in the retinal tissue as well as the overexpression of high mobility group box-1 and the overactivation of the NLRP3 inflammasome. Furthermore, quercetin inhibited the overexpression of TLR4 and NF-κBp65, reduced the expression of the pro-angiogenic vascular endothelial growth factor and soluble intercellular adhesion molecule-1, and upregulated the neurotrophins brain-derived neurotrophic factor and nerve growth factor. Intraperitoneal injection of the heme oxygenase-1 inhibitor zinc protoporphyrin blocked the protective effect of quercetin. These findings suggest that quercetin exerts therapeutic effects in diabetic retinopathy possibly by inducing heme oxygenase-1 expression. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 2016PS229K) on April 8, 2016.

Key words: angiogenesis, diabetic retinopathy, flavonoid, heme oxygenase-1, inflammation, neurotrophin, quercetin, repair