木樨草素对弗氏佐剂诱导大鼠关节炎的改善作用及其机制  

Protective mechanism of luteolin on adjuvant-induced arthritis in rats

作　　者：施凤超[1] 朱文峰[1] 朱宇伟 王成[1] 周敦[1] SHI Fengchao;ZHU Wenfeng;ZHU Yuwei;WANG Cheng;ZHOU Dun(Department of Orthopaedics,Yancheng Third People’s Hospital/Affiliated Hospital 6 of Nantong University,Jiangsu 224001)

机构地区：[1]盐城市第三人民医院/南通大学第六附属医院骨科,江苏224001

出　　处：《交通医学》2021年第4期342-346,共5页Medical Journal of Communications

基　　金：江苏省中医药局(YB2017073)。

摘　　要：目的:探讨木樨草素对佐剂诱导大鼠关节炎的改善作用及其可能机制。方法:采用佐剂注射大鼠左足建立关节炎模型,分为正常对照组、弗氏佐剂性关节炎(AA)组、双氯芬酸钠(DS)组、木樨草素20(Lu 20)组和Lu 40组,每组10只。实验第21~28天,每日DS组大鼠口服双氯芬酸钠5 mg/kg,Lu 20组和Lu 40组分别口服木樨草素20 mg/kg和40 mg/kg。采用排水法检测大鼠左后足踝关节体积(HPV),酶联免疫法检测大鼠血清及滑膜液中细胞因子水平,观察大鼠滑膜病理改变,采用蛋白印迹法检测大鼠滑膜组织HMGB1/TLR/NF-κB相关蛋白表达。结果:AA组注射弗氏佐剂后第7、14、21天左后足HPV进行性升高,与正常对照组相比,差异均有统计学意义(P<0.01)。注射佐剂后第28天Lu 20组、Lu 40组及DS组大鼠左后足HPV明显减小,与AA组相比,差异均有统计学意义(P<0.01),但Lu 20组、Lu 40组、DS组3组间比较,差异均无统计学意义(P>0.05)。与正常对照组相比,AA组大鼠血清及滑膜液中IL-6、IL-1β和TNF-α水平显著升高,差异均有统计学意义(P<0.01)。Lu 20组、Lu 40组及DS组大鼠血清及滑膜液中IL-6、IL-1β和TNF-α水平明显低于AA组,差异均有统计学意义(P<0.01),而Lu 20组、Lu 40组、DS组3组间比较,差异均无统计学意义(P>0.05)。AA组大鼠踝关节出现明显的滑膜水肿、炎性细胞浸润、上皮变性和关节软骨糜烂。与AA组相比,Lu 20组、Lu 40组及DS组大鼠关节滑膜水肿、炎性细胞浸润、上皮变性及关节软骨糜烂明显减轻。Lu 20组、Lu 40组、DS组病理改变无明显差异。与正常对照组比较,AA组大鼠滑膜组织中HMGB1、TLR4、MyD88、p-NF-κB-p65(P-P65)和p-IκBα蛋白表达水平显著上调;与AA组比较,Lu 20组、Lu 40组及DS组大鼠滑膜组织中上述蛋白水平明显下调,而Lu 20组、Lu 40组、DS组之间无明显差异。结论:木樨草素可显著改善佐剂诱导的大鼠关节炎,其机制可能与调控HMGB1/TLR/NF-κBObjective:To explore the ameliorative effect of luteolin on adjuvant-induced arthritis in rats and its possible mechanism.Methods:Arthritis model was established by injecting adjuvant into the left foot of rats,which were divided into the normal control group,Freund’s adjuvant arthritis(AA)group,diclofenac sodium(DS)group,luteolin 20 group(Lu 20)and Lu 40 group,with 10 rats in each group.On the 21st to 28th day of the experiment,rats in DS group were given diclofenac sodium 5 mg/kg,and luteolin 20 mg/kg and luteolin 40 mg/kg respectively.The left hind foot ankle joint volume(HPV)of rats was measured by drainage method,the cytokine levels in serum and synovial fluid of rats were measured by enzyme-linked immunosorbent assay,the pathological changes of rat synovium were observed,and the expression of HMGB1/TLR/NF-κB related protein in rat synovial tissue was detected by western blot method.Results:The HPV of left hind foot in AA group increased progressively on the 7th,14th and 21st day after injection of Freund’s adjuvant,and the difference was statistically significant compared with the normal control group(P<0.01).On the 28th day after adjuvant injection,HPV in left hind foot of rats in Lu 20,Lu 40 and DS groups decreased significantly compared with AA group(P<0.01),but there was no significant difference among Lu 20,Lu 40 and DS groups(P>0.05).Compared with the normal control group,the levels of IL-6,IL-1βand TNF-αin serum and synovial fluid of the AA rats were significantly higher,and the differences were statistically significant(P<0.01).The levels of IL-6,IL-1βand TNF-αin serum and synovial fluid of rats in Lu 20,Lu 40 and DS groups were significantly lower than those in the AA group(P<0.01).There were obvious synovial edema,inflammatory cell infiltration,epithelial degeneration and articular cartilage erosion in ankle joint of AA rats.Compared with the AA group,synovial edema,inflammatory cell infiltration,epithelial degeneration and articular cartilage erosion of rats in Lu 20,Lu 40 and DS groups

关 键 词：木樨草素 弗氏佐剂诱导关节炎 HMGB1/TLR/NF-κB相关蛋白 大鼠 

分 类 号：R684.3[医药卫生—骨科学]