瑞香素调节STING/TBK1/IRF3信号通路对脓毒症大鼠免疫炎症反应的影响  

Effects of daphnetin modulating STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats

作　　者：温亚[1] 李燕[1] 白思怡 陈凯林[1] 成丽英[1] 李亚冬[1] WEN Ya;LI Yan;BAI Siyi;CHEN Kailin;CHENG Liying;LI Yadong(Department of Emergency Medicine,Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院急诊医学科,山西太原030001

出　　处：《西安交通大学学报（医学版）》2024年第5期822-827,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：山西省科技厅重点研发项目(No.201903D321017)。

摘　　要：目的探究瑞香素调节STING/TBK1/IRF3信号通路对脓毒症大鼠免疫炎症反应的影响。方法选用80只雄性Sprague Dawley(SD)大鼠,将大鼠随机分为4组,假手术组20只;其余60只按照盲肠结扎穿刺法(CLP)构建脓毒症小鼠模型,腹腔注射不同剂量瑞香素,分为无瑞香素模型组(0 mg/kg)、低剂量组(2.5 mg/kg)、高剂量组(5 mg/kg),每组20只;模型组及假手术组腹腔注射等量0.1%DMSO。观察CLP建模后的各组大鼠存活率。收集肺、肾、肝和脾组织进行病理组织学分析。ELISA检测大鼠血清炎症因子(TNF-α、IL-6、IL-1β),流式细胞术检测外周血中的T淋巴细胞亚群,Western blotting检测STING/TBK1/IRF3信号通路蛋白表达变化。结果与假手术组相比,模型组大鼠生存率降低(P<0.05),各个脏器组织损伤明显,血清炎症因子(TNF-α、IL-6、IL-1β)水平上升(P<0.05),外周血CD4^(+)比例、CD4^(+)/CD8^(+)比值均降低(P<0.05),CD8^(+)比例、Th1/Th2比值均升高(P<0.05),STING、p-TBK1/TBK1、p-IRF3/IRF3蛋白表达均下调(P<0.05)。与模型组相比,瑞香素高剂量组提高了大鼠生存率(P<0.05),各脏器组织损伤明显减轻,血清炎症因子水平降低(P<0.05),外周血CD4^(+)比例、CD4^(+)/CD8^(+)比值升高(P<0.05),CD8^(+)比例、Th1/Th2比值降低(P<0.05),STING、p-TBK1/TBK1、p-IRF3/IRF3蛋白表达升高(P<0.05)。结论瑞香素可通过调节STING/TBK1/IRF3信号通路,改善脓毒症大鼠免疫炎症反应。Objective To explore the effects of dapnetin’s regulation of STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats.Methods In this study,80 male Sprague Dawley(SD)rats were selected and randomly divided into four groups,20 rats in the sham-operation group,the remaining 60 mice with sepsis were constructed according to cecal ligation puncture(CLP)method and were intraperitoneally injected with different doses of dapnetin.They were divided into no-dapnetin model group(0 mg/kg),low-dose group(2.5 mg/kg),and high-dose group(5 mg/kg),with 20 mice in each group.The model group and sham-operation group were intraperitoneally injected with 0.1%DMSO.The survival rate of rats in each group after 72 h of CLP modeling was observed.Lung,kidney,liver and spleen tissues were collected for histopathological analysis.Serum inflammatory factors(TNF-α,IL-6,and IL-1β)were detected by ELISA,T lymphocyte subsets in peripheral blood were detected by flow cytometry,and STING/TBK1/IRF3 signaling pathway protein expression was detected by Western blotting.Results Compared with sham-operation group,the survival rate of rats in model group was reduced(P<0.05),each organ tissue injury was significant,serum inflammatory factors(TNF-α,IL-6,and IL-1β)levels were increased(P<0.05),CD4^(+)ratio and CD4^(+)/CD8^(+)ratio in peripheral blood were decreased(P<0.05),while CD8^(+)ratio and Th1/Th2 ratio were increased(P<0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were downregulated(P<0.05).Compared with the model group,dapnetin in high-dose group improved the survival rate of rats(P<0.05),the injury of all organs and tissues was reduced,and the level of serum inflammatory factors was decreased(P<0.05),CD4^(+)ratio and CD4^(+)/CD8^(+)r atio in peripheral blood were increased(P<0.05),while CD8^(+)ratio and Th1/Th2 ratio were decreased(P<0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were increased(P<0.05).Conclusion Dapnetin can improve the immune inflammatory response of sepsis

关 键 词：瑞香素 脓毒症 盲肠结扎穿刺(CLP) STING/TBK1/IRF3信号通路 免疫调节 炎症 

分 类 号：R285.5[医药卫生—中药学]