秦皮苷调节SDF-1/CXCR4信号通路对类风湿关节炎大鼠炎性反应的影响  

Effects of fraxin on inflammatory response in rats with rheumatoid arthritis by regulating SDF-1/CXCR4 signaling pathway

作　　者：韩天然 纪青灼 王小玉 吴琳 邰立仕 李泽光[4] HAN Tianran;JI Qingzhuo;WANG Xiaoyu;WU Lin;TAI Lishi;LI Zeguang(The First Clinical School of Medicine,Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 124000,China;Acupuncture and Rehabilitation Center,Qingdao Hiser Hospital of Qingdao University,Qingdao,Shandong 266000,China;Department of Neurology,Hanji Minkang TCM Internal Medicine Clinic,Baoding,Hebei 072550,China;Department of Rheumatology,The First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 124000,China)

机构地区：[1]黑龙江中医药大学第一临床医学院,黑龙江哈尔滨124000 [2]青岛大学附属青岛市海慈医院针推康复中心,山东青岛266000 [3]韩记民康中医内科诊所神经内科,河北保定072550 [4]黑龙江中医药大学附属第一医院风湿科,黑龙江哈尔滨124000

出　　处：《湖南中医药大学学报》2025年第3期402-408,共7页Journal of Hunan University of Chinese Medicine

基　　金：黑龙江省自然科学基金项目(2023085J08)。

摘　　要：目的探讨秦皮苷调节基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)信号通路对类风湿性关节炎(RA)大鼠炎性反应的影响。方法大鼠随机分为正常组、RA组、秦皮苷低剂量(0.2 g/kg)组、秦皮苷高剂量(0.4 g/kg)组、秦皮苷高剂量(0.4 g/kg)+NUCC-390(2.2 mg/kg)组,每组10只。除正常组外,其余各组以Ⅱ型胶原诱导建立RA模型。干预后检测各组大鼠关节炎指数(AI)与足容积;Micro-CT扫描检测踝关节骨质形态;HE染色观察踝关节组织病理形态;ELISA法检测血清与关节液炎症因子白细胞介素(IL)-6、IL-18、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)、类风湿因子(RF)水平;Western blot检测踝关节组织SDF-1、CXCR4蛋白表达水平。结果与正常组比较,RA组大鼠AI,足容积,骨破坏评分,踝关节组织病理形态学评分,IL-6、IL-18、TNF-α、CRP、RF水平及SDF-1、CXCR4蛋白表达水平均升高(P<0.05);与RA组比较,秦皮苷低、高剂量组AI,足容积,骨破坏评分,踝关节组织病理形态学评分,IL-6、IL-18、TNF-α、CRP、RF水平及SDF-1、CXCR4蛋白表达水平均降低(P<0.05),且秦皮苷高剂量组各指标水平相比秦皮苷低剂量组降低(P<0.05);与秦皮苷高剂量组比较,秦皮苷高剂量+NUCC-390组AI,足容积,骨破坏评分,踝关节组织病理形态学评分,IL-6、IL-18、TNF-α、CRP、RF水平及SDF-1、CXCR4蛋白表达水平均升高(P<0.05)。结论秦皮苷可通过下调SDF-1/CXCR4信号通路减轻RA大鼠炎性反应并改善其关节炎症状。Objective To investigate the effects of fraxin on inflammatory response in rats with rheumatoid arthritis(RA)by regulating stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods Rats were randomly divided into normal group,RA group,low-dose(0.2 g/kg)fraxin group,high-dose(0.4 g/kg)fraxin group,high-dose(0.4 g/kg)fraxin+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.The RA model was established with type II collagen induction in all groups except the normal group.After the intervention,the arthritis index(AI)and paw volume of rats in each group were measured.Micro-CT scanning was performed to assess the bone morphology of the ankle joints.Histopathological morphology of the ankle joint tissue was observed using HE staining.ELISA was used to test the levels of inflammatory cytokines interleukin(IL)-6,IL-18,tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),and rheumatoid factor(RF)in the serum and synovial fluid.Western blot was performed to measure the protein expression levels of SDF-1 and CXCR4 in the ankle joint tissue.Results Compared with the normal group,the RA group exhibited increased levels of AI,paw volume,bone destruction score,histopathological morphological score of the ankle joint,and the levels of IL-6,IL-18,TNF-α,CRP,RF,as well as the protein expression levels of SDF-1 and CXCR4(P<0.05).Compared with the RA group,both the low-dose and high-dose fraxin groups showed decreased levels of AI,paw volume,bone destruction score,histopathological morphological score of the ankle joint,and the levels of IL-6,IL-18,TNF-α,CRP,RF,as well as the protein expression levels of SDF-1 and CXCR4(P<0.05).Furthermore,the high-dose fraxin group exhibited lower levels of these indicators compared to the low-dose fraxin group(P<0.05).Compared with the high-dose fraxin group,the high-dose fraxin+NUCC-390 group showed increased levels of AI,paw volume,bone destruction score,histopathological morphological score of the ankle joint,and the levels of IL-6,IL-18,TNF-α,CRP,RF,

关 键 词：类风湿关节炎 秦皮苷 基质细胞衍生因子-1 CXC趋化因子受体4 炎性反应 

分 类 号：R285.5[医药卫生—中药学]