摘要
目的观察祛寒逐风合剂对胶原诱导型关节炎(collagen induced arthritis,CIA)大鼠的影响,并探讨其作用机制。方法SD大鼠随机分出12只作为正常组,其余65只采用尾根部皮下注射胶原乳剂制备CIA大鼠模型。将造模成功的60只大鼠随机分为模型组,甲氨蝶呤组,祛寒逐风合剂低、中、高剂量组,连续4周灌胃相应药物。实验期间测定足跖肿胀度和关节炎指数(AI)。给药4周后,HE染色观察踝关节组织病理学变化;ELISA检测血清C-反应蛋白(CRP)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1、IL-1β、IL-6水平;Western blot检测膝关节滑膜组织中Janus激酶2(JAK2)、信号转导和转录激活因子3(STAT3)、磷酸化JAK2(p-JAK2)、p-STAT3蛋白表达;RT-qPCR检测膝关节滑膜组织中JAK2、STAT3 mRNA水平;免疫组化检测基质金属蛋白酶(MMP)-1、MMP-3、MMP-13表达。结果与模型组比较,祛寒逐风合剂中、高剂量均能降低大鼠足跖肿胀度,改善踝关节病理变化,减少血清中CRP、TNF-α、IL-1、IL-1β、IL-6等炎症因子的分泌(P<0.01),下调滑膜组织中JAK2、STAT3的蛋白与mRNA表达,以及p-JAK2/JAK2、p-STAT3/STAT3水平(P<0.05),抑制踝关节中MMP-1、MMP-3、MMP-13的阳性表达(P<0.01)。结论祛寒逐风合剂可有效改善类风湿关节炎模型大鼠足跖肿胀度、踝关节病理变化与炎症因子分泌,其作用机制可能与调控JAK2/STAT3信号通路有关。
Objective To observe the effects of Quhan Zhufeng mixture on Collagen Induced Arthritis(CIA)rats and explore its mechanism.Methods Twelve SD rats were reserved as control group,and the rest rats were injected with collagen emulsion subcutaneously at the tail root to prepare CIA rat model.The 60 rats who were successfully modeled were randomly divided into the model group,methotrexate group,and low-,medium-and high-dose groups of Quhan Zhufeng mixture,and the corresponding drugs were given by gavage for 4 consecutive weeks.Foot swelling and arthritis index(AI)were measured during the experiment.After 4 weeks of administration,the histopathological changes of ankle joint were observed by HE staining.Serum CRP,TNF-α,IL-1,IL-1βand IL-6 levels were detected by ELISA.Western blot was used to detect the expressions of JAK2,STAT3,p-JAK2 and p-STAT3 proteins in synovial tissue of knee joint.RT-qPCR was used to detect JAK2 and STAT3 mRNA in synovial tissue of knee joint.The expression of MMP-1,MMP-3 and MMP-13 was determined by immunohistochemistry.Results Compared with the model group,medium-and high-dose of Quhan Zhufeng mixture could reduce the foot swelling of CIA rats,improve the pathological changes of ankle joints and reduce the secretion of inflammatory factors such as CRP,TNF-α,IL-1,IL-1β,and IL-6 in serum(P<0.01);down-regulate the mRNA and protein expression of JAK2、STAT3、p-JAK2/JAK2、p-STAT3/STAT3 in synovial tissue(P<0.05),and inhibit the positive expression of MMP-1,MMP-3 and MMP-13 in ankle joint(P<0.01).Conclusion Quhan Zhufeng mixture can effectively improve the foot swelling,ankle joint pathological changes and inflammatory factor secretion in RA model rats,and its mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.
作者
苏小军
郭影
朱文菊
王欢
何倩
张志明
田雪梅
刘亚鹏
沈海丽
马骏
包强
SU Xiaojun;GUO Ying;ZHU Wenju;WANG Huan;HE Qian;ZHANG Zhiming;TIAN Xuemei;LIU Yapeng;SHEN Haili;MA Jun;BAO Qiang(Gansu Provincial Hospital of TCM,Lanzhou 730050,China;Gansu University of Chinese Medicine,Lanzhou 730030,China;Lanzhou Institute for Food and Drug Control,Lanzhou 730050,China;The Second Hospital&Clinical Medical School,Lanzhou University,Lanzhou 730030,China;Pharmacology Laboratory of Chinese Materia Medica-third-level TCM Laboratory Assessed by SATCM,Lanzhou 730000,China)
出处
《中国中医基础医学杂志》
2025年第8期1373-1378,共6页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金项目(82260880)
甘肃省自然科学基金项目(22JR5RA626)
甘肃省卫生健康行业科技创新重大科研项目(GSWSZD2025-08)。
