摘要
目的:缺氧是类风湿关节炎(RA)发展的重要因素,本研究旨在探究红景天苷改善RA模型小鼠缺氧和缓解炎症反应的效果和潜在机制。方法:C57BL/6小鼠被用于构建胶原蛋白诱导的关节炎(CIA)模型小鼠,并随机分为空白组、模型组、对照组、实验组。HE染色用于评价滑膜组织病理改变。采用实时荧光定量聚合酶链式反应、酶联免疫吸附测定,探究红景天苷对炎症反应、氧化应激以及脯氨酰羟化酶结构域蛋白2(PHD2)/蛋白磷酸酶2A(PP2A)/促分裂素原活化蛋白激酶(MAPK)信号的调节。结果:与空白组相比,模型组、对照组、实验组滑膜组织存在显著的炎性浸润和缺氧反应。与模型组相比,实验组的HE染色结果表明红景天苷能明显抑制滑膜组织增殖和炎症细胞浸润(P<0.01)。ELISA结果表明红景天苷可以抑制促炎因子中肿瘤坏死因子、白介素-6的表达(P<0.01)。RT-qPCR结果显示红景天苷能够抑制缺氧诱导因子-1α并上调核因子E2相关因子2水平(P<0.01),抑制PHD2/PP2A/MAPK信号通路的激活(P<0.01)。结论:红景天苷能抑制CIA小鼠炎性反应和缺氧损伤,缓解RA的潜在机制与抑制PHD2/PP2A/MAPK信号通路激活相关。
Objective:Hypoxia is an important factoRin development of rheumatoid arthritis(RA).Aimed to explore effect and potential mechanism of salidroside in alleviating hypoxia and inflammatory response in RA mice models.Methods:C57BL/6 mice were used to construct collagen-induced arthritis(CIA)mice model,and then were randomly divided into blank group,model group,control group,and experimental group.HE staining was used to evaluate synovial histological changes.Real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to investigate regulation of salidroside on inflammatory response,oxidative stress and prolyl hydroxylase domain protein 2(PHD2)/protein phosphatase 2A(PP2A)/mitogen-activated protein kinase(MAPK)signals.Results:Compared with the blank group,the synovial tissue of model group,control group and experimental group had significant inflammatory infiltration and hypoxia reaction.Compared with the model group,the experimental group showed that salidroside could significantly alleviate arthritis symptoms and reduce synovial hyperplasia(P<0.01).ELISA results showed that salidroside could inhibit the expression of pro-inflammatory factors TNF-αand IL-6(P<0.01).RT-qPCRresults showed that salidroside could inhibit the level of hypoxia inducing factor-1αand up-regulate the level of nucleaRfactoRE2-related factoR2(P<0.01),as well as inhibit the activation of PHD2/PP2A/MAPK signaling pathway(P<0.01).Conclusion:Salidroside can inhibit the inflammatory response and hypoxic injury in CIA mice.The potential mechanism in alleviating RA related to inhibiting the activation of PHD2/PP2A/MAPK signaling pathway.
作者
张文广
李琴
星媛
ZHANG Wenguang;LI Qin;XING Yuan(Rheumatology Department,Qinghai Hospital of Traditional Chinese Medicine,Xining 810001,China)
出处
《陕西中医》
CAS
2024年第3期323-327,共5页
Shaanxi Journal of Traditional Chinese Medicine
基金
青海省卫生健康系统重点课题(2022-WJZD-04)。
