摘要
目的观察鼠麴草对大鼠痛风性关节炎的治疗作用及对NALP3炎性体信号通路的影响。方法将60只大鼠随机分为正常对照组,模型对照组,鼠麴草醇提物小剂量、中剂量、大剂量组,秋水仙碱组。除正常对照组外,其他各组制作痛风性关节炎模型。造模同时,正常对照组和模型对照组给予0.9%氯化钠溶液灌胃,鼠麴草小剂量、中剂量、大剂量组分别给予鼠麴草醇提物0.4,0.8,1.6 g·kg^-1灌胃,秋水仙碱组给予秋水仙碱0.97 mg·kg^-1灌胃。每次2 mL,连续8 d。给药后检测不同时间大鼠足跖肿胀率,酶联免疫吸附(ELISA)法测定大鼠血清中尿酸(UA)、黄嘌呤氧化酶(XOD)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α),蛋白免疫印迹法(Western blotting)检测关节组织NALP3、凋亡相关斑点样蛋白(ASC)、半胱天冬酶-1(caspase-1)表达,苏木精-伊红(HE)染色观察大鼠膝关节组织病理变化。结果与正常对照组比较,模型对照组大鼠足跖肿胀率明显升高(P<0.01),血清UA、XOD、IL-1β、TNF-α含量显著升高(P<0.01),滑膜组织NALP3、ASC、Caspase-1表达显著增加(P<0.01),踝关节滑膜组织大量炎症细胞浸润,细胞增生明显;鼠麴草醇提物小剂量、中剂量、大剂量组大鼠踝关节肿胀率均显著降低(P<0.01或P<0.05),血清UA、XOD、IL-1β、TNF-α含量显著降低(P<0.01或P<0.05),滑膜组织NALP3、ASC、Caspase-1蛋白表达显著降低(P<0.01),关节组织炎性浸润及细胞组织增生程度明显减轻。结论鼠麴草对大鼠痛风性关节炎有治疗作用,其机制可能是通过抑制NALP3炎性体相关蛋白表达,抑制XOD活性,降低血中UA、IL-1β、TNF-α的生成来减轻关节炎症反应。
Objective To observe the therapeutic effect of Gnaphaliumaffine D.Don on rat models with gouty arthritis and the effects on NALP3 inflammasomes(NACHT-LRR-PYD-containing protein-3,NALP3)-related signaling pathways.Methods Sixty rats were randomly divided into normal control group,model control group,low-dose group,medium-dose group,high-dose group of Gnaphaliumaffine,and colchicine group.Except the normal control group,a rat model of acute gouty arthritis was made by injecting sodium urate into the right ankle joint cavity of the hind limb.The normal control group and the model control group were given 0.9%sodium chloride solution by gavage.In the low-dose group,medium-dose group and high-dose group,rats were given 0.4,0.8,1.6 g·kg^-1,respectively.And colchicine group was given colchicine 0.97 mg·kg^-1 by gavage.In each group,the volume was 2 mL,once per day for 8 days.After the administration,the rat paw swelling rate at different time periods was measured.The uric acid(UA),xanthine oxidase(XOD),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in serum of each group were measured by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of NLRP3,apoptosis-related speckle-like protein(ASC),and caspase-1 in joint tissues.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of knee joints in each group of rats.Results Compared with the normal control group,the swelling rate of the ankle joint was significantly increased(P<0.01 or P<0.05).The contents of UA,XOD,IL-1βand TNF-αin the serum of the rats were significantly increased(P<0.01).The expressions of NALP3,ASC and Caspase-1 in synovial tissue were significantly increased(P<0.01),a large number of inflammatory cells infiltrated into the synovial tissue of ankle joint,and the cell proliferation was obvious.In the low-dose group,medium-dose group and high-dose groups of Gnaphaliumaffine,Gnaphaliumaffine could significantly reduce the swelling rate of the ankle joints in rats(P<0.01 or P<0.05)
作者
黄蕾
杨全伟
夏俊锋
刘新国
HUANG Lei;YANG Quanwei;XIA Junfeng;LIU Xinguo(Department of Pharmacy,the First Hospital of Wuhan,Wuhan 430022,China;Public Inspection and Testing Center of Xiantao City,Hubei Province,Xiantao 433000,China)
出处
《医药导报》
CAS
北大核心
2020年第11期1477-1481,共5页
Herald of Medicine
基金
湖北省卫生与计划生育委员会资助项目(WJ2017M180)。
