目的 探讨青葙苷Ⅰ通过活性氧（ROS）介导核因子 κB p65（NF-κB p65）/核苷酸结合寡聚化结构域样受 体蛋白 3（NLRP3）/胱天蛋白酶Ⅰ（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。方法 选 取无特定病原体动物（SPF）健康雄性新西兰大白兔 24 只，随机分为假手术组、模型组、甲钴胺组以及青葙苷 Ⅰ组，每组 6 只。假手术组仅切开球结膜，其余 3 组复制视神经损伤模型。假手术组与模型组均给予等体积双 蒸水灌胃，甲钴胺组给予浓度 0.15 mg·kg-1甲钴胺水溶液灌胃，青葙苷Ⅰ组给予浓度 30 mg·kg-1青葙苷Ⅰ水溶 液灌胃，每日给药一次，连续给药 28 d。给药结束后采用耳鼻喉科内窥镜检测各组给药后眼底情况；苏木精- 伊红染色法（HE）观察各组视网膜情况；脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）检测各组 视网膜节细胞凋亡情况；免疫荧光（IF）法检测视网膜组织 ROS、NF-κB、NLRP3 及 Caspase-1 的荧光表达；免 疫印迹法（Western Blot）法检测 ROS、NF-κB p65、NLRP3、Caspase-1、焦孔素 D（GSDMD）蛋白表达；采用透 视电镜扫描检测各组焦亡小体数量。结果 与模型组比较，甲钴胺组与青葙苷Ⅰ组视网膜凋亡指数降低（P＜ 0.05）；与甲钴胺组比较，青葙苷Ⅰ组视网膜凋亡指数降低（P＜0.05）。免疫荧光结果显示，与假手术组比较， 模型组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1 蛋白表达升高（P＜0.05）；与模型组比较，甲钴胺组 与青葙苷Ⅰ组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1 蛋白表达降低（P＜0.05）；与甲钴胺组比较， 青葙苷Ⅰ组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1 蛋白表达较低（P＜0.05）。Western Blot 结果显 示，与假手术组比较，模型组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1、GSDMD 蛋白表达升高（P＜ 0.05）；与模型组比较，甲钴胺组与青葙苷Ⅰ组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1、GSDMD 蛋 白表达降低（P＜0.05）；与甲钴胺组比较，青葙苷Ⅰ组视网膜组织 ROS、NF-κB p65、NLRP3、Caspase-1、 GSDMD 蛋白表达较低（P＜0.05）；与假手术组比较，模型组节细胞焦亡小体数量明显增多（P＜0.05）。与模型 组比较，甲钴胺组与青葙苷Ⅰ组焦亡小体数量减少（P＜0.05）；与甲钴胺组比较，青葙苷Ⅰ组焦亡小体数量 减少（P＜0.05）。结论 青葙苷Ⅰ可以抑制 ROS 的产生，抑制 NF-κB p65/NLRP3/Caspase-1 信号通路，减少 GSDMD 的分解释放，进而减少视神经节细胞的焦亡发生，减轻视神经损伤，延缓视力损失。

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.

R285.5

国家资助博士后研究人员计划项目（GZC20231025）；辽宁省自然科学基金博士科研启动计划项目（2025-BS-0711）；辽宁省针灸养生 康复重点实验室项目（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）。