青蒿琥酯通过IL-23/IL-17信号通路对实验性自身免疫性葡萄膜炎大鼠模型的干预作用OA
Interventional effect of artesunate on the rat model of experimental autoim-mune uveitis via the interleukin-23/interleukin-17 signaling pathway
目的 探讨青蒿琥酯(ART)通过白细胞介素(IL)-23/IL-17信号通路对实验性自身免疫性葡萄膜炎大鼠模型的干预作用.方法 将48只Lewis雌性大鼠随机分为正常对照组、EAU模型组、低浓度ART组、中浓度ART组、高浓度ART组、曲安奈德(TA)组,除正常对照组外,其余各组均诱导EAU,ART各浓度组大鼠造模前2 d使用不同浓度ART玻璃体内注药处理,TA组大鼠于造模前2 d使用TA玻璃体内注药,正常对照组不做任何处理.观察造模后第1、4、7、14、21天前房炎症变化,造模后第14、21天通过HE染色进行组织病理学检查,采用Western blot检测各组大鼠视网膜组织中IL-23、IL-17、IL-12蛋白表达水平.结果 眼部炎症评分:造模后第1、4、7、14、21天,EAU模型组大鼠均明显高于正常对照组,高浓度ART组和TA组均明显低于EAU模型组(均为P＜0.05),低浓度、中浓度ART组与EAU模型组比较差异均无统计学意义(均为P＞0.05).视网膜病理组织切片评分:造模后第14、21天,EAU组大鼠均明显高于正常对照组,造模后第14天,高浓度ART组明显低于EAU模型组(均为P＜0.05).与正常对照组相比,EAU模型组大鼠在造模后第14、21天的IL-23、IL-17、IL-12蛋白相对表达水平均显著升高(均为P＜0.05).与EAU模型组相比,高浓度ART组和TA组大鼠在造模后第14天均明显降低(均为P＜0.05).与EAU模型组相比,造模后第21天,TA干预能有效降低三种因子的表达(均为P＜0.05).结论 500 g·L-1 ART的干预能显著减轻EAU模型的炎症反应,明显降低IL-23、IL-17、IL-12的表达,进而抑制IL-23/IL-17信号通路活化,提示ART的抗炎机制可能与IL-23/IL-17信号通路有关.
Objective To investigate the interventional effect of artesunate(ART)on rat models of experimental au-toimmune uveitis(EAU)via the interleukin(IL)-23/IL-17 signaling pathway.Methods Totally 48 female Lewis rats were randomly divided into the normal control group,EAU model group,low-concentration ART group,medium-concentration ART group,high-concentration ART group,and triamcinolone acetonide(TA)group.Except for the normal control group,EAU was induced in all other groups.Rats in each ART concentration group received intravitreal injection of corresponding concentrations of ART 2 days before model establishment;rats in the TA group received intravitreal TA injection at the same time point,while the normal control group received no treatment.Anterior chamber inflammatory changes were observed on days 1,4,7,14 and 21 post-induction.Histopathological examination was performed via hematoxylin-eosin staining on days 14 and 21 post-induction.Western blot was used to detect the protein expression levels of IL-23,IL-17 and IL-12 in retinal tissues of rats in each group.Results Ocular inflammation scores:on days 1,4,7,14 and 21 post-induction,scores in the EAU model group were significantly higher than those in the normal control group,while scores in the high-concentration ART group and TA group were significantly lower than those in the EAU model group(all P＜0.05).No statistically significant differences were found between the low-concentration and medium-concentration ART groups and the EAU model group(all P＞0.05).Retinal histopathological section scores:on days 14 and 21 post-induction,scores in the EAU group were sig-nificantly higher than those in the normal control group.On day 14 post-induction,scores in the high-concentration ART group were significantly lower than those in the EAU model group(all P＜0.05).Compared with the normal control group,the relative protein expression levels of IL-23,IL-17 and IL-12 in the EAU model group significantly increased on days 14 and 21 post-induction(all P＜0.05).Compared with the EAU model group,these levels markedly decreased in the high-concen-tration ART group and TA group on day 14 post-induction(all P＜0.05).On day 21 post-induction,TA intervention signifi-cantly reduced the expression of the three cytokines compared with the EAU model group(all P＜0.05).Conclusion In-tervention with 500 g·L-1 ART can significantly alleviate inflammatory responses in the EAU model and markedly reduce the expression of IL-23,IL-17 and IL-12,thereby inhibiting the activation of the IL-23/IL-17 signaling pathway.These findings suggest that the anti-inflammatory mechanism of ART may be associated with the IL-23/IL-17 signaling pathway.
刘晓娟;郝晓凤;赵伟伟;杜改萍
266102 山东省青岛市,解放军海军第971医院崂山医疗区眼科100040 北京市,中国中医科学院眼科医院266102 山东省青岛市,解放军海军第971医院崂山医疗区眼科266100 山东省青岛市,解放军海军第971医院眼科
医药卫生
青蒿琥酯实验性自身免疫性葡萄膜炎白细胞介素-23白细胞介素-17白细胞介素-12
artesunateexperimental autoimmune uveitisinterleukin-23interleukin-17interleukin-12
《眼科新进展》 2026 (6)
450-453,472,5
青岛市医药卫生科研计划项目(编号:2024-WJKY22)
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