Chu Fang-Fang, Zhao Yan-Song, Zhao Yu-Ze, Bai Chen, Xiao Pei-Lun, Wang Xiao-Li, Yu Shu-Na, Jiang Ji-Ying
Department of Anatomy, Weifang Medical College, Weifang, Shandong 261053, China; Ophthalmology Center, Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2023 Jun 15;25(6):645-652. doi: 10.7499/j.issn.1008-8830.2301036.
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.
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.
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 (<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (<0.05).
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.
研究褪黑素（Mel）对新生小鼠氧诱导视网膜病变（OIR）的保护作用及高迁移率族蛋白B1（HMGB1）/核因子κB（NF-κB）/NLRP3炎性小体轴的作用。
将7日龄新生C57BL/6J小鼠随机分为对照组、模型组（OIR组）和褪黑素治疗组（OIR+Mel组），每组9只。采用高氧诱导法建立OIR模型。苏木精-伊红染色及视网膜铺片制备用于观察视网膜结构和新生血管形成。免疫荧光染色用于检测与HMGB1/NF-κB/NLRP3轴及淋巴细胞抗原6G相关的蛋白质和炎性因子表达。比色法用于检测髓过氧化物酶活性。
OIR组视网膜结构破坏，无灌注区大且有新生血管形成，而OIR+Mel组视网膜结构破坏改善，新生血管形成及无灌注区减少。与对照组相比，OIR组与HMGB1/NF-κB/NLRP3轴相关的蛋白质和炎性因子表达、淋巴细胞抗原6G表达及髓过氧化物酶活性显著增加（<0.05）。与OIR组相比，OIR+Mel组上述指标显著降低（<0.05）。与对照组相比，OIR组视网膜中褪黑素受体表达显著降低（<0.05）。与OIR组相比，OIR+Mel组褪黑素受体表达显著增加（<0.）。
Mel可通过抑制HMGB1/NF-κB/NLRP3轴减轻新生小鼠OIR诱导的视网膜损伤，并可能通过褪黑素受体途径发挥作用。
