复方芩柏颗粒通过调控Claudin-1表达及JAK2/STAT3信号通路缓解小鼠溃疡性结肠炎  

Compound Qinbai Granule relieving ulcerative colitis in mice by regulating Claudin-1 expression and JAK2/STAT3 signaling pathway

作　　者：王晓燕[1] 肖超[1] 王真权[1] 肖佑[1] WANG Xiaoyan;XIAO Chao;WANG Zhenquan;XIAO You(The Second Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410005,China)

机构地区：[1]湖南中医药大学第二附属医院,湖南长沙410005

出　　处：《湖南中医药大学学报》2025年第3期417-424,共8页Journal of Hunan University of Chinese Medicine

基　　金：湖南省中医药管理局课题(B2023095,C2024017);湖南中医药大学校级课题(2022XYLH031)。

摘　　要：目的探讨复方芩柏颗粒在溃疡性结肠炎(UC)治疗中的作用机制,研究其对炎症反应、氧化应激、肠道黏膜屏障功能及Janus激酶2(JAK2)/信号转导与转录激活因子3(STAT3)信号通路的调控作用。方法采用2,4,6三硝基苯磺酸/乙醇灌肠法构建C57B/L小鼠UC模型,随机分为UC模型组、抑制剂组、奥沙拉嗪组和复方芩柏颗粒组;正常对照组小鼠灌肠等体积生理盐水,每组6只。通过HE染色法观察结肠组织病理损伤情况,免疫组织化学染色法检测密封蛋白-1(Claudin-1)蛋白表达水平,ELISA法测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)等氧化应激相关因子以及肿瘤坏死因子-α(TNF-α)、白细胞介素(interleukin,IL)-6、IL-10、IL-12、IL-4和转化生长因子-β(TGF-β)等炎症因子水平,RT-qPCR和Western blot分别检测Claudin-1、JAK2、STAT3 mRNA与蛋白表达情况。结果与正常对照组相比,UC模型组CMDI、DAI值,MDA、TNF-α、IL-6、IL-12含量,JAK2、STAT3 mRNA相对表达量,p-JAK2/JAK2、p-STAT3/STAT3蛋白表达量均升高(P<0.05);SOD活性,CAT、GSH、IL-10、TGF-β、IL-4含量,Claudin-1表达水平均降低(P<0.05)。与UC模型组相比,奥沙拉嗪组和复方芩柏颗粒组CMDI、DAI值,MDA、TNF-α、IL-6、IL-12含量,JAK2、STAT3 mRNA相对表达量,p-JAK2/JAK2、p-STAT3/STAT3蛋白表达量均降低(P<0.05);SOD活性,CAT、GSH、IL-10、TGF-β、IL-4含量,Claudin-1表达水平均升高(P<0.05)。结论复方芩柏颗粒通过调节氧化应激、炎症反应和肠道屏障功能,抑制JAK2/STAT3信号通路的激活,从而治疗UC。Objective To explore the mechanism of action of Compound Qinbai Granule(CQBG)in treating ulcerative colitis(UC)and to study its regulatory effects on inflammatory response,oxidative stress,intestinal mucosal barrier function,and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods The UC model of C57B/L mice was established by 2,4,6-trinitrobenzenesulfonic acid/ethanol enema method and the mice were randomly divided into normal control,UC model,inhibitor,olsalazine,and CQBG groups.Mice in the normal control group received an enema of saline of equal volume.Each group consisted of six mice.The pathological damage of colon tissue was observed by HE staining,the protein expression level of Claudin-1 was determined by immunohistochemical staining,and the levels of oxidative stress-related factors such as superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA),as well as inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-10,IL-12,and transforming growth factor-β(TGF-β),were measured by ELISA.The mRNA and protein expression of Claudin-1,JAK2,and STAT3 were determined by RT-qPCR and Western blot,respectively.Results Compared with the normal control group,the CMDI and DAI scores,the levels of MDA,TNF-α,IL-6,and IL-12,the relative expression levels of JAK2 and STAT3 mRNA,and the protein expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 in the UC model group increased(P<0.05),while the SOD activity,the levels of CAT,GSH,IL-10,TGF-β,and IL-4,the protein and mRNA expression levels of Claudin-1,and the protein expression level of Claudin-1 in the UC model group decreased(P<0.05).Compared with the UC model group,the CMDI and DAI scores,the levels of MDA,TNF-α,IL-6,and IL-12,the relative expressions of JAK2 and STAT3 mRNA,and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 in the inhibitor,olsalazine,and CQBG groups decreased(P<0.05),while the SOD activity,the levels of CAT,GSH,IL-10,TGF-β,and IL-4,and the protein and m

关 键 词：溃疡性结肠炎 JAK2/STAT3信号通路 氧化应激 炎症 肠道黏膜屏障功能 

分 类 号：R285.5[医药卫生—中药学]