基于CXCL13/PI3K/Akt通路探究二妙散对胶原诱导性关节炎小鼠的影响  

Effect of Ermiao San on Mice with Collagen-induced Arthritis Based on the CXCL13/PI3K/Akt Pathway

作　　者：杨家祥 黄柳云 覃亮[3] 王艳君[4] 王亭亭 贾松涛 沈向楠 崔书国[4] 唐艳阁[4] YANG Jiaxiang;HUANG Liuyun;TAN Liang;WANG Yanjun;WANG Tingting;JIA Songtao;SHEN Xiangnan;CUI Shuguo;TANG Yange(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Zhejiang Chinese Medical University,Hangzhou 310053,China;Affiliated Hospital of Hebei University,Baoding 071000,China;Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Gaocheng People′s Hospital of Shijiazhuang City,Shijiazhuang 052100,China)

机构地区：[1]河北中医药大学,河北石家庄050200 [2]浙江中医药大学,浙江杭州310053 [3]河北大学附属医院,河北保定071000 [4]河北省中医院,河北石家庄050011 [5]石家庄市藁城人民医院,河北石家庄052100

出　　处：《河北中医药学报》2025年第2期50-56,共7页Journal of Hebei Traditional Chinese Medicine and Pharmacology

基　　金：河北省中医药管理局科研计划项目(2022057、2023317)。

摘　　要：目的:探究二妙散(Ermiao San,EMS)对胶原诱导性关节炎(Collagen-induced Arthritis,CIA)小鼠的治疗作用并分析其机制。方法:40只DBA/1J小鼠按照随机数字表法取8只作为正常组(NC组),32只小鼠建立CIA模型。将造模成功的小鼠随机分为模型组(CIA组)、EMS组、甲氨蝶呤组(MTX组)。各组按照相对应的药物进行灌胃,且连续干预4周。观察各组小鼠关节炎指数(AI)评分、各组小鼠滑膜组织进行相关检测:HE染色、Tunel染色、增殖细胞的相关抗原Ki67、趋化因子CXC配体13(CXCL13)/磷酸肌醇3′-激酶(PI3K)/蛋白激酶B(Akt)通路相关蛋白和基因表达、凋亡相关蛋白表达。结果:与NC组比较,CIA组小鼠AI评分增加,滑膜组织出现炎症细胞浸润、滑膜增生、血管翳生成等表现,滑膜组织细胞凋亡率下降、增殖率增加,CXCL13/PI3K/Akt信号通路相关PI3K、Akt、p-Akt和糖原合成酶激酶-3(GSK-3β)蛋白表达增加,CXCL13和CXC基序趋化因子受体5(CXCR5)基因表达上调,凋亡相关蛋白:半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)和Bax表达降低,Bcl2表达增加。与CIA组相比,EMS组与MTX组小鼠AI评分下降,滑膜病理切片炎症细胞减少、滑膜和血管翳生成减少,滑膜组织细胞凋亡率升高,增殖率降低,CXCL13/PI3K/Akt信号通路相关蛋白PI3K、Akt、p-Akt和GSK-3β蛋白表达下降,CXCL13和CXCR5基因表达下调;凋亡相关蛋白Caspase-3和Bcl-2相关X蛋白(Bax)表达增加,B淋巴细胞瘤-2基因(Bcl2)表达降低。EMS组和MTX两者相比无统计学差异。结论:EMS对CIA鼠关节肿胀、滑膜组织炎症具有一定改善作用,其效应机制可能与CXCL13/PI3K/Akt通路调节相关。Objective:To explore the therapeutic effect of Ermiao San(EMS)on mice with collagen-induced arthritis(CIA)and analyze its mechanism.Methods:Among 40 DBA/1J mice,8 were selected as the normal group(NC group)according to the random number table method,and 32 mice were used to establish the CIA model.The successfully modeled mice were randomly divided into the model group(CIA group),the EMS group,and the methotrexate group(MTX group).Each group was gavaged with the corresponding drug and intervened continuously for 4 weeks.The arthritis index(AI)scores of the mice in each group were observed,and relevant tests were carried out on the synovial tissues of the mice in each group:hematoxylin-eosin(HE)staining,Tunel staining,the expression of the proliferation-associated antigen Ki67 of proliferating cells,the related proteins and genes of the chemokine CXC ligand 13(CXCL13)/phosphatidylinositol 3′-kinase(PI3K)/protein kinase B(Akt)pathway,and the expression of apoptosis-related proteins.Results:Compared with the NC group,the AI score of the mice in the CIA group increased;In the synovial tissues,manifestations such as infiltration of inflammatory cells,synovial hyperplasia,and pannus formation were observed;The apoptosis rate of synovial tissue cells decreased,and the proliferation rate increased;The protein expressions of PI3K,Akt,p-Akt,and GSK-3βrelated to the CXCL13/PI3K/Akt signaling pathway increased;The gene expressions of CXCL13 and CXC CXCR5 were upregulated;The expressions of apoptosis-related proteins,including Caspase-3 and Bax decreased,while the expression of Bcl2 increased.Compared with the CIA group,the AI scores of the mice in the EMS group and the MTX group decreased;In the pathological sections of the synovium,the number of inflammatory cells decreased,and the formation of synovium and pannus was reduced;The apoptosis rate of synovial tissue cells increased,and the proliferation rate decreased;The protein expressions of PI3K,Akt,p-Akt,and GSK-3βrelated to the CXCL13/PI3K/Akt signaling pathway decre

关 键 词：类风湿关节炎 二妙散 胶原诱导性关节炎 CXCL13/PI3K/Akt通路 

分 类 号：R285.5[医药卫生—中药学]