摘要
目的 探讨汉黄芩素(wogonin,Wog)调节核因子(nuclear factor,NF)红系2相关因子(NF-erythroid 2-related factor,Nrf2)/Toll样受体(Toll like receptor,TLR)4/NF-κB通路对膝骨关节炎(knee osteoarthritis,KOA)大鼠的影响。方法 将SD大鼠随机分为正常组、模型组、Wog低、中及高剂量(10、30及90 mg/kg)组,阳性对照组(塞来昔布,24 mg/kg),每组10只,用木瓜蛋白酶建立KOA大鼠模型,灌胃28 d。检测大鼠机械痛和冷痛阈值、软骨病理变化、细胞凋亡、炎症因子、氧化应激和蛋白表达水平。结果 在术后D7、D14、D21、D28,较模型组,Wog中、高剂量组和阳性对照组机械痛阈值、冷痛阈值显著上升;软骨病理损伤显著好转;细胞凋亡率、白介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子(tumor necrosis factor,TNF)-α、丙二醛、半胱氨酸天冬氨酸蛋白酶(caspase)-3和caspase-9、基质金属蛋白酶(matrix metallopeptidase,MMP)-1和MMP-13、TLR4蛋白水平以及核/总NF-κB p65蛋白比值均显著降低;超氧化物歧化酶、谷胱甘肽过氧化酶活性、Nrf2以及血红素加氧酶-1蛋白水平均显著增加(P <0.01)。结论 Wog减轻KOA大鼠炎性损伤的机制可能与上调Nrf2表达及抑制TLR4/NF-κB活化有关。
Objective To investigate the effects of wogonin(Wog)on knee osteoarthritis(KOA)in rats by regulating nuclear factor(NF)-erythroid 2-related factor(Nrf2)/Toll like receptor 4(TLR4)/NF-κB signaling pathway.Methods SD rats were randomly divided into normal group,model group,Wog low,medium and high dose(10,30 and 90 mg/kg)groups,and positive control group(celecoxib,24 mg/kg),with 10 rats in each group.KOA model was established by gavage of papain for 28 days.The mechanical and cold pain thresholds,pathological changes of cartilage,cell apoptosis,inflammatory factors,oxidative stress and protein expression levels were detected.Results At postoperative D7,D14,D21,and D28,compared with the model group,the mechanical pain threshold and cold pain threshold of Wog medium and high dose groups and positive control group were significantly increased.Pathological damage of cartilage was significantly improved.Cell apoptosis rate,interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,malondialdehyde,caspase-3,caspase-9,matrix metalloproteinase(MMP)-1,MMP-13,TLR4 protein level and the ratio of nuclear/total NF-κB p65 protein were significantly decreased.The activities of superoxide dismutase,glutathione peroxidase,Nrf2 and heme oxygenase-1 protein were significantly increased(P<0.01).Conclusion The mechanism of Wog reducing inflammatory damage in KOA rats may be related to upregulating Nrf2 expression and inhibiting TLR4/NF-κB activation.
作者
李会东
杨学钰
郭文帆
郑雪君
卢吉高
杨勇
LI Huidong;YANG Xueyu;GUO Wenfan;ZHENG Xuejun;LU Jigao;YANG Yong(Department of Sports Medicine,Zhangjiakou Second Hospital,Zhangjiakou 075000,Hebei Province,China)
出处
《世界临床药物》
CAS
2023年第6期552-560,共9页
World Clinical Drug
