银屑平丸调节cGAS-STING信号通路对银屑病小鼠的保护作用

Protective effect of Yinxieping pill on psoriasis mice by regulating cGAS-STING signaling pathway

目的:探讨银屑平丸调节GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对银屑病小鼠的保护作用。方法:取C57BL/6小鼠以咪喹莫特(IMQ)诱导银屑病模型,随机分为模型组、银屑平丸组、联合组,每组10只,另取10只C57BL/6小鼠作为对照组。用银屑平丸和RocA分组干预小鼠,检测其银屑病症状。HE染色检测小鼠皮肤组织病理变化;免疫组化染色检测各组小鼠皮肤组织中性粒细胞浸润情况;检测小鼠血清促炎因子与抗炎因子水平;免疫印迹法检测小鼠皮肤组织cGAS-STING通路蛋白表达。结果:与对照组相比,模型组小鼠皮肤组织发生明显病理损伤,银屑病皮损面积及严重程度指数(PASI)、抓痒次数、皮肤表皮层厚度、髓过氧化物酶(MPO)阳性表达,IL-1β、IL-6、IL-17、IL-23及cGAS与STING蛋白表达升高,IL-4、TGF-β、IL-10水平降低,差异有统计学意义(均P<0.05)。与模型组比较,银屑平丸组小鼠皮肤组织病理损伤减轻,PASI、抓痒次数、皮肤表皮层厚度、MPO阳性表达、IL-1β、IL-6、IL-17、IL-23水平及cGAS与STING蛋白表达降低,IL-4、TGF-β及IL-10升高,差异有统计学意义(均P<0.05)。楝酰胺可减弱银屑平丸对银屑病小鼠的作用。结论:银屑平丸通过阻止cGAS-STING信号通路激活传导而减轻银屑病小鼠免疫炎症,改善其皮肤组织损伤症状,发挥保护作用。

Objective:To explore the protective effect of Yinxieping pill on psoriasis mice by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signaling pathway.Methods:C57BL/6 mice were selected to induce psoriasis model with imiquimod(IMQ),and randomly separated into model group,Yinxieping pill group,combination group,10 mice in each group.Additional 10 C57BL/6 mice were included as control group.After intervention with Yinxieping pill and RocA of mice in each group,symptoms of psoriasis were detected.HE staining was applied to detect pathological changes in mouse skin tissue.Immunohistochemical staining was applied to detect infiltration of neutrophils in skin tissue of mice in each group.Levels of pro-inflammatory and anti-inflammatory factors in mouse serum were detected.Immunoblotting was applied to detect expression of cGAS-STING pathway proteins in mouse skin tissue.Results:Compared with the control group,the skin tissue of mice in the model group showed obvious pathological damage,PASI,number of scratching,thickness of the epidermis of the skin,myeloperoxidase positive expression,IL-1β,IL-6,IL-17 and IL-23 levels,cGAS and STING protein expression were obviously increased,and IL-4,TGF-βand IL-10 levels were obviously reduced,difference statistically significant(all P<0.05).Compared with the model group,the pathological damage of the skin tissue of mice in the Yinxieping pill group was reduced,PASI,number of scratching,thickness of the epidermis of the skin,myeloperoxidase positive expression,IL-1β,IL-6,IL-17 and IL-23 levels,cGAS and STING protein expression were reduced,and IL-4,TGF-βand IL-10 levels were increased,difference statistically significant(all P<0.05).Rocaglamide A can weaken the effect of Yinxieping pill on psoriasis mice.Conclusion:Yinxieping pill can alleviate immune inflammation in psoriasis mice by blocking activation and transmission of cGAS-STING signaling pathway,thereby improving their skin tissue damage symptoms and exerting a protective effect.