中药新药与临床药理2026，Vol.37Issue(5)：836-847,12.DOI:10.19378/j.issn.1003-9783.2026.05.007
青葙苷Ⅰ通过活性氧介导NF-κB p65/NLRP3/Caspase-1信号通路抑制视神经损伤模型视神经节细胞焦亡的机制
Celosin I Inhibitting Pyroptosis of Retinal Ganglion Cells in an Optic Nerve Injury Model via the ROS-Mediated NF-κB/NLRP3/Caspase-1 Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism by which celosin Ⅰ inhibits pyroptosis of retinal ganglion cells in an optic nerve injury model via reactive oxygen species(ROS)-mediated regulation of the NF-κB p65/NLRP3/Caspase-1 signaling pathway.Methods Twenty-four specific pathogen-free(SPF)healthy male New Zealand white rabbits were randomly divided into a sham-operated group,a model group,a mecobalamin group,and a celosin Ⅰ group,with 6 rabbits in each group.In the sham-operated group,only the conjunctiva was incised,while optic nerve injury models were established in the other three groups.The sham-operated and model groups were administered an equal volume of double-distilled water by gavage.The mecobalamin group received a 0.15 mg·kg-1 aqueous solution of mecobalamin,and the celosin Ⅰ group received a 30 mg·kg-1 aqueous solution of celosin Ⅰ,administered once daily for 28 days.After the administration period,fundus conditions were examined using an otorhinolaryngology endoscope.Retinal morphology in each group was observed using hematoxylin-eosin(HE)staining.Apoptosis of retinal ganglion cells was detected using the TdT-mediated dUTP nick end labeling(TUNEL)assay.Fluorescence expression of ROS,NF-κB,NLRP3,and Caspase-1 in retinal tissue was assessed by immunofluorescence(IF).Protein expression levels of ROS,NF-κB p65,NLRP3,Caspase-1,and gasdermin D(GSDMD)were measured by Western Blot.The number of pyroptotic bodies in each group was examined using transmission electron microscopy.Results Compared with the model group,the retinal apoptosis index was significantly decreased in both the mecobalamin and celosin Ⅰ groups(P＜0.05);furthermore,compared with the mecobalamin group,the celosin Ⅰ group exhibited a significantly decreased retinal apoptosis index(P＜0.05).Immunofluorescence results showed that compared with the sham-operated group,the expression levels of ROS,NF-κB p65,NLRP3,and Caspase-1 proteins in retinal tissue were significantly increased in the model,mecobalamin,and celosin I groups(P＜0.05).Compared with the model group,the expression levels of these proteins were significantly decreased in the mecobalamin and celosin I groups(P＜0.05).Moreover,compared with the mecobalamin group,the celosin I group showed significantly lower expression levels of ROS,NF-κB p65,NLRP3,and Caspase-1 proteins in retinal tissue(P＜0.05).Western Blot results indicated that compared with the sham-operated group,the expression levels of ROS,NF-κB p65,NLRP3,Caspase-1,and GSDMD proteins in retinal tissue were significantly increased in the model group(P＜0.05).Compared with the model group,the expression levels of these proteins were significantly decreased in the mecobalamin and celosin Ⅰ groups(P＜0.05).Compared with the mecobalamin group,the celosin Ⅰ group exhibited significantly lower expression levels of ROS,NF-κB p65,NLRP3,Caspase-1,and GSDMD proteins in retinal tissue(P＜0.05).Compared with the sham-operated group,the number of pyroptotic bodies in retinal ganglion cells was significantly increased in the model group(P＜0.05).Compared with the model group,the number of pyroptotic bodies was significantly reduced in the mecobalamin and celosin Ⅰ groups(P＜0.05);additionally,compared with the mecobalamin group,the celosin Ⅰgroup showed a significantly lower number of pyroptotic bodies(P＜0.05).Conclusion Celosin Ⅰ can inhibit ROS production,thereby suppressing the NF-κB/NLRP3/Caspase-1 signaling pathway,reducing the cleavage and release of GSDMD,subsequently decreasing pyroptosis of retinal ganglion cells,alleviating optic nerve injury,and delaying vision loss.关键词
青葙苷Ⅰ/活性氧/视神经细胞/焦亡/视神经损伤模型/NF-κB p65/NLRP3/Caspase-1信号通路/兔Key words
celosin Ⅰ/reactive oxygen species/retinal ganglion cells/pyroptosis/optic nerve injury model/NF-κB/NLRP3/Caspase-1 signaling pathway/rabbits分类
医药卫生引用本文复制引用
韩易言,左韬,赵磊,宁志豪,董宝强,郑曲..青葙苷Ⅰ通过活性氧介导NF-κB p65/NLRP3/Caspase-1信号通路抑制视神经损伤模型视神经节细胞焦亡的机制[J].中药新药与临床药理,2026,37(5):836-847,12.基金项目
国家资助博士后研究人员计划项目(GZC20231025) （GZC20231025）
辽宁省自然科学基金博士科研启动计划项目(2025-BS-0711) （2025-BS-0711）
辽宁省针灸养生康复重点实验室项目(18-006-0-06) （18-006-0-06）
辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金资助项目(zyzx2410). （zyzx2410）
