基于HMGB1/NF-κB/NLRP3轴探讨褪黑素对氧诱导视网膜病变的保护作用

doi:10.7499/j.issn.1008-8830.2301036

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摘要目的观察褪黑素（melatonin，Mel）对新生小鼠氧诱导视网膜病变（oxygen-induced retinopathy，OIR）的保护作用，并探讨HMGB1/NF-κB/NLRP3轴在其中的作用。方法 7日龄C57BL/6J新生小鼠随机分为对照组、模型组（OIR组）及Mel处理组（OIR+Mel组），各组n=9。采用高氧诱导法制备OIR模型。苏木精-伊红染色和视网膜铺片法检测视网膜结构和新生血管；免疫荧光染色法检测HMGB1/NF-κB/NLRP3轴相关蛋白和炎性因子及淋巴细胞抗原6G表达；比色法检测髓过氧化物酶活性。结果 OIR组视网膜结构被破坏，出现大片无灌注区和新生血管，OIR+Mel组可见破坏的视网膜结构改善，新生血管和无灌注区减少。与对照组相比，OIR组HMGB1/NF-κB/NLRP3轴相关蛋白和炎性因子表达升高（均P<0.05），淋巴细胞抗原6G表达和髓过氧化物酶活性升高（均P<0.05）；Mel处理后，上述各指标降低（均P<0.05）。与对照组相比，OIR组视网膜中褪黑素受体表达降低；Mel处理后，褪黑素受体表达较OIR组升高（均P<0.05）。结论 Mel可能通过抑制HMGB1/NF-κB/NLRP3轴减轻OIR新生小鼠视网膜损伤，且可能通过褪黑素受体途径发挥作用。

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	褚芳芳
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	肖培伦
	王晓莉
	于树娜
	蒋吉英

关键词 ：褪黑素, 氧诱导视网膜病变, HMGB1/NF-κB/NLRP3轴, 炎症, 新生小鼠

Abstract：Objective To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. Methods Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. Results The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). Conclusions Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Key words： Melatonin Oxygen-induced retinopathy HMGB1/NF-κB/NLRP3 axis Inflammation Neonatal mouse

收稿日期: 2023-01-12

基金资助:山东省自然科学基金（ZR2022MH011）；山东省医药卫生科技发展计划项目（202001020642）；国家自然科学基金（82071888）。

通讯作者: 蒋吉英，女，教授，Email：jiangjy@wfmc.edu.cn E-mail: jiangjy@wfmc.edu.cn

作者简介: 褚芳芳，女，硕士研究生；

引用本文:

褚芳芳,赵岩松,赵玉泽等. 基于HMGB1/NF-κB/NLRP3轴探讨褪黑素对氧诱导视网膜病变的保护作用[J]. 中国当代儿科杂志, 2023, 25(6): 645-652.

CHU Fang-Fang,ZHAO Yan-Song,ZHAO Yu-Ze et al. Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis[J]. CJCP, 2023, 25(6): 645-652.

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http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2301036 或 http://www.zgddek.com/CN/Y2023/V25/I6/645

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