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  

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

作　　者：褚芳芳 赵岩松[2] 赵玉泽 白晨 肖培伦 王晓莉[3] 于树娜[1] 蒋吉英[1] 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)

机构地区：[1]潍坊医学院人体解剖学教研室,山东潍坊261053 [2]潍坊医学院附属医院眼科中心,山东潍坊261031 [3]潍坊医学院医学影像学院,山东潍坊261053

出　　处：《中国当代儿科杂志》2023年第6期645-652,共8页Chinese Journal of Contemporary Pediatrics

基　　金：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)。

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。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.

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 

分 类 号：R774.1[医药卫生—眼科]