Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis

CHU Fang-Fang; ZHAO Yan-Song; ZHAO Yu-Ze; BAI Chen; XIAO Pei-Lun; WANG Xiao-Li; YU Shu-Na; JIANG Ji-Ying

doi:10.7499/j.issn.1008-8830.2301036

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Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (6) : 645-652. DOI: 10.7499/j.issn.1008-8830.2301036

EXPERIMENTAL RESEARCH

Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis

CHU Fang-Fang, ZHAO Yan-Song, ZHAO Yu-Ze, BAI Chen, XIAO Pei-Lun, WANG Xiao-Li, YU Shu-Na, JIANG Ji-Ying

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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

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CHU Fang-Fang, ZHAO Yan-Song, ZHAO Yu-Ze, BAI Chen, XIAO Pei-Lun, WANG Xiao-Li, YU Shu-Na, JIANG Ji-Ying. Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(6): 645-652 https://doi.org/10.7499/j.issn.1008-8830.2301036

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