目的：评估外用白介素(Interleukin, IL)-6特异性抑制剂托珠单抗滴眼液在调控角膜碱烧伤后修复的安全性和有效性。方法：6只角膜假烧伤小鼠局部使用托珠单抗滴眼(2.5 mg/mL)和6只角膜假烧伤小鼠局部使用生理盐水滴眼，分别作为实验组和空白组以评估托珠单抗滴眼液的安全性。30只碱烧伤小鼠，按照1∶1随机分配到治疗组和对照组，治疗组使用托珠单抗滴眼液滴眼，对照组使用生理盐水，每日6次，连续用14 d。通过前段光学相干断层扫描观察虹膜前粘连、角膜后弹力层脱离及角膜水肿，在体视显微镜下检查角膜瘢痕形成及上皮伤口愈合。在角膜切片上评估IL-6定位、肌成纤维细胞、免疫细胞浸润和角膜上皮化生。在角膜铺片上评估角膜新生血管和新生淋巴管面积。通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction, qRT-PCR)方法检测小鼠角膜 IL-6的表达水平。结果：对未进行碱烧伤的角膜使用托珠单抗治疗未观察到明显的角膜结构的损伤。角膜碱烧伤后可见角膜结构的破坏，角膜瘢痕形成并伴有角膜上皮伤口的延迟愈合。使用托珠单抗治疗后，虹膜前粘连的发生率从86.67%下降至20%(P <0.01)，角膜后弹力层脱离的发生率从93.33%下降至53.33%(P <0.05)，角膜厚度小于对照组[(100.03±15.73)μ m vs. (207.02±56.30)μ m，P＜0.001]，角膜混浊评分从对照组的3.76±0.44下降到治疗组的1.94±0.83(P <0.001)，治疗组在第5天(P <0.05)、第10天(P <0.001)和第14天(P <0.001)的上皮愈合率高于对照组。角膜碱烧伤后可见IL-6大量分布于角膜全层，且可见大量肌成纤维细胞形成及免疫细胞浸润，托珠单抗治疗后抑制了IL-6的表达(下降77.5%，P <0.05)，肌成纤维细胞数量从每视野(91.44±65.60)个减少至(12.89±10.51)个(P <0.01)，免疫细胞的数量从每视野(60.30±28.71)个细胞减少至每视野(6.80±3.82)个细胞(P <0.001)。此外，托珠单抗还减少角膜切片中每视野的杯状细胞数目由(11.3±5.29)个减少至(2.0±1.90个)(P <0.01)，并减少角膜新生血管和新生淋巴管的形成(分别减少了76.86%和71.16%，均P <0.001)。结论：局部使用托珠单抗抑制IL-6未见明显角膜毒性，且可以调控角膜碱烧伤后的修复。

Objective: To evaluate the safety and effect of topical IL-6 inhibitor tocilizumab eye drops in regulating corneal alkali burn repair. Methods: Six mice without corneal burns were locally treated with tocilizumab eye drops (2.5 mg/mL) and six mice with corneal pseudo burn were treated with saline, respectively, as experimental and blank groups to evaluate the safety of tocilizumab eye drops. 30 alkali burned mice were randomly divided into a treatment group and a control group in a 1:1 ratio. The treatment group received tocilizumab eye drops, while the control group received physiological saline solution 6 times per day for 14 days. Observe the anterior adhesion of the iris, detachment of the Descemet membrane, and corneal edema through anterior segment optical coherence tomography (AS-OCT), and examine corneal scarring and epithelial wound healing under a stereomicroscope. Evaluate IL-6 localization, myofibroblasts, immune cell infiltration, and corneal epithelial metaplasia on corneal sections. Evaluate corneal neovascularization and neovascularization area by whole-mount cornea staining. Detect the expression level of IL-6 in mouse cornea by qRT-PCR. Results: No significant damage to the corneal structure was observed in the treatment of unburned corneas with tocilizumab. After corneal alkali burns, the corneal structure was damaged, corneal scarring was formed, and delayed healing of corneal epithelial wounds was observed.After treatment with tocilizumab, the incidence of anterior synechia of the iris significantly decreased from 86.67% to 20% (P <0.01), the incidence of Descemet membrane detachment decreased from 93.33% to 53.33% (P <0.05), the corneal thickness was significantly less than that of the control group (100.03±15.73) μ m vs. (207.02±56.30)μ m (P <0.001), the corneal opacity score decreased from 3.76±0.44 in the control group to 1.94±0.83 in the treatment group (P <0.001), and the epithelial healing rate in the treatment group was significantly higher than that in the control group on day 5 (P <0.05), day 10 (P <0.001), and day 14 (P <0.001).After corneal alkali burns, IL-6 was distributed throughout the corneal layer, and a large number of myofibroblasts and immune cells were observed. After treatment with tocilizumab, the expression of IL-6 was inhibited (decreased by 77.5%, P <0.05), the number of myofibroblasts decreased from (91.44±65.60) per field to (12.89±10.51) per field (P <0.01), and the number of immune cells decreased from (60.30±28.71) cells per field to (6.80±3.82) cells per field (P <0.001). In addition, tocilizumab also reduced the number of goblet cells per field in corneal sections (from 11.3±5.29 to 2.0±1.90) (P <0.01), and reduced the formation of corneal neovascularization and neovascular lymphatic vessels (by 76.86% and 71.16%, respectively, both P <0.001). Conclusion: Topical use of tocilizumab to inhibit IL-6 showed no significant corneal toxicity and can regulate the repair of cornea after alkali burns.

目的：探究间歇性禁食(intermittent fasting, IF)对内毒素诱导小鼠葡萄膜炎(endotoxin-induced uveitis, EIU)的保护作用及其可能的抗炎机制。方法：小鼠随机分为对照组(Ctr)、EIU组及IF+EIU组。16∶8禁食方案(9 : 00—17 : 00进食)。对照组行玻璃体腔内注射磷酸盐缓冲溶液(phosphate buffered saline, PBS)，其余两组行玻璃体腔内脂多糖注射。建模后监测小鼠空腹血糖及体质量。光学相干断层扫描和苏木精伊红染色观察评估炎症水平。视网膜铺片行神经炎症相关的观察评价。BV2细胞分为Ctr组，LPS组及饥饿+内毒素组，蛋白印迹及实时荧光定量逆转录PCR技术检测相关蛋白及mRNA表达水平。结果：①IF对体质量无明显影响，可引起血糖显著降低随后逐渐恢复。病程中期起IF干预下小鼠视网膜水肿恢复，玻璃体腔内炎性渗出比EIU组显著减少(P＜0.01)。IF逆转LPS诱导的小胶质细胞激活，减轻视网膜神经节细胞及神经纤维损伤(P＜0.05)。②饥饿培养抑制LPS诱导的BV2细胞的磷酸化信号转导与转录激活因子1和3及诱导型一氧化氮合酶( inducible nitric oxide synthase, iNOS)的蛋白表达水平(P＜0.05)，显著降低iNOS、白介素-6等炎症因子的表达水平。结论：IF能够加速EIU炎症的消退，减轻组织结构的炎性破坏，抑制小胶质细胞的促炎型激活。

Objective: To investigate the protective effects of intermittent fasting (IF) on endotoxin-induced uveitis in mice and its potential anti-inflammatory mechanisms. Methods: Mice were randomly divided into three groups: control group (Ctr), endotoxin-induced uveitis (EIU) group, and IF + EIU group. The IF regimen followed a 16:8 fasting scheme (feeding from 9:00 to 17:00). The control group received intravitreal injections of PBS, while the other two groups received intravitreal injections of lipopolysaccharide (LPS). After modeling, fasting blood glucose and body weight of the mice were monitored. Inflammation levels were assessed using OCT and H&E staining. Retinal flat mounts were used for evaluating neuroinflammation. BV2 cells were divided into Ctr group, LPS group, and starvation (LG) + LPS group. The expression levels of related proteins and mRNA were detected using WB and RT-qPCR. Results: IF had no significant effect on body weight but caused a significant decrease in blood glucose, which gradually recovered. From the middle stage of the disease, mice in the IF intervention group show edretinal edema recovery, significantly reduced intravitreal inflammatory exudation and cell infiltration compared to the EIU group (P <0.01). IF reversed LPS-induced microglial activation and significantly alleviated damage to retinal ganglion cells and nerve fibers (P <0.05). Starvation culture significantly inhibited LPS-induced expression levels of p-STAT1/3 and iNOS proteins in BV2 cells (P <0.05) and significantly reduced the expression levels of inflammatory factors such as iNOS and IL-6. Conclusion: IF can accelerate the resolution of EIU inflammation, reduce inflammatory damage to tissue structures, and inhibit pro-inflammatory activation of microglia.