基于Hepcidin和JAK2/STAT3信号通路探讨通痹颗粒 对胶原诱导性关节炎大鼠的影响  

Effects of Tongbi Granule on collagen-induced arthritis rats based on Hepcidin and JAK2/STAT3 signaling pathway

作　　者：吴伊莹[1,2] 柳玉佳[1] 廖亮英[1] 范伏元[1] 郭志华[2] WU Yiying;LIU Yujia;LIAO Liangying;FAN Fuyuan;GUO Zhihua(The First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医药大学学报》2024年第6期960-966,共7页Journal of Hunan University of Chinese Medicine

基　　金：湖南省自然科学基金项目(2020JJ5434,2023JJ40508);湖南省教育厅科研项目(21B0370);湖南省卫生健康委科研项目(202103101094,20201816);湖南省中医药管理局基金项目(D2022123)。

摘　　要：目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响。方法选取36只雌性SD大鼠随机分成空白组、模型组、阳性对照组和通痹颗粒低、中、高剂量组,每组6只。空白组不予处理,其余组用牛Ⅱ型胶原建立CIA模型。造模完成后,空白组、模型组予生理盐水灌胃,其余各组分别以巴瑞替尼片和低、中、高剂量通痹颗粒灌胃。每天1次,连续4周。HE染色行滑膜组织病理学观察;酶联免疫吸附法测定血清Hepc、白细胞介素6(interleukin 6,IL-6)水平;逆转录-聚合酶链反应法测定滑膜中JAK2、STAT3、细胞信号因子传导抑制体(suppressor of cytokine signaling,SOCS)1、SOCS3的mRNA相对表达量;Western blot法检测滑膜中JAK2、p-JAK2、STAT3、p-STAT3、SOCS1、SOCS3的蛋白表达量。结果模型组见滑膜上皮结构缺损,滑膜重度增生,排列紊乱,并有大量炎症细胞浸润和多个血管翳形成;各给药组滑膜炎症均有所减轻,阳性对照组优于通痹颗粒高剂量组,通痹颗粒中、高剂量组优于低剂量组。与模型组相比,各给药组关节炎指数评分、血清Hepc和IL-6水平均显著降低(P<0.01);与阳性对照组相比,通痹颗粒中、低剂量组关节炎指数评分、血清Hepc和IL-6水平均升高(P<0.05)。与模型组比较,阳性对照组和通痹颗粒低、中、高剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均降低(P<0.05),而通路抑制因子SOCS1、SOCS3 mRNA和蛋白的表达均升高(P<0.05);与阳性对照组比较,通痹颗粒各剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均升高(P<0.05),而SOCS1、SOCS3 mRNA和蛋白的表达均降低(P<0.05)。结论通痹颗粒能够改善CIA大鼠滑膜炎症,其机制可能与抑制JAK2/STAT3信号通路而减少Hepc的表达Objective To study the effects of Tongbi Granule on hepcidin(Hepc)and janus kinase(JAK)2/signal transduction and activator of transcription(STAT)3 signaling pathway in collagen-induced arthritis(CIA)rats.Methods A total of 36 female SD rats were randomized into blank,model,positive control,low-,medium-,and high-dose of Tongbi Granule groups,with six rats in each group.CIA model was constructed with bovine typeⅡcollagen in all groups except the blank group.After modeling,the blan and model groups were given normal saline by gavage,the other groups were given baricitinib tablets,and low-,medium-,and high-dose of Tongbi Granule by gavage respectively,once a day,for continual four weeks.HE staining was performed to observe pathological synovial tissue.Serum Hepc and interleukin 6(IL-6)levels were measured by ELISA.The mRNA relative expressions of JAK2,STAT3,suppressor of cytokine signaling(SOCS)1,and SOCS3 in synovium were determined by RT-PCR.Western blot was used to test the protein expressions of JAK2,p-JAK2,STAT3,p-STAT3,SOCS1 and SOCS3 in synovium.Results In the model group,there were defects of synovial epithelium,severe synovial hyperplasia,disordered arrangement,and a large number of inflammatory cell infiltration and pannus formation.However,all administration groups showed reduction of synovial inflammation,the positive control group was better than the high-dose Tongbi Granule group,and the medium-and high-dose groups was better than the low-dose group.Compared with model group,arthritis index scores,and levels of serum Hepc and IL-6 were significantly lower in all drug administration groups(P<0.01).Compared with the positive control group,the arthritis index scores,serum Hepc and IL-6 levels in low-and medium-dose Tongbi Granule groups were higher(P<0.05).Compared with model group,the mRNA and protein expressions of JAK2 and STAT3,as well as the protein expressions of p-JAK2 and p-STAT3 were lower(P<0.05),while the mRNA and protein expressions of pathway inhibitors SOCS1 and SOCS3 were higher in positiv

关 键 词：类风湿关节炎 胶原诱导性关节炎 中药 通痹颗粒 铁调素 JAK2/STAT3信号通路 

分 类 号：R285[医药卫生—中药学]