富马酸二甲酯对急性痛风性关节炎大鼠的保护作用及其机制研究  

Study on the protective effect of dimethyl fumarate on acute gouty arthritis in rats and its mechanism

作　　者：王国镇[1] 刘紫佳 唐铎 周志祥[2] 张铁[1] Wang Guozhen;Liu Zijia;Tang Duo;Zhou Zhixiang;Zhang Tie(Department of Clinical Laboratory,China-Japan Friendship Hospital,Beijing 100029,China;College of Chemistry and Life Sciences,Beijing University of Technology,Beijing 100124,China;China Meat Products Comprehensive Research Center,Beijing Food Science Research Institute,Beijing 100068,China)

机构地区：[1]中日友好医院检验科,北京100029 [2]北京工业大学化学与生命科学学院,北京100124 [3]北京食品科学研究院中国肉类食品综合研究中心,北京100068

出　　处：《中国医药》2025年第4期550-555,共6页China Medicine

基　　金：国家自然科学基金(42077399);北京市朝阳区科技计划项目(CYSF1930、CYSF2224)。

摘　　要：目的研究富马酸二甲酯(DMF)对急性痛风性关节炎大鼠的保护作用并探讨其作用机制。方法21只雄性SD大鼠在无特定病原体环境下饲养1周后完全随机分为生理盐水组、尿酸盐结晶(MSU)组和MSU+DMF组,每组7只。生理盐水组不造模,生理盐水灌胃;MSU组和MSU+DMF组以MSU制作急性痛风性关节炎模型,分别以生理盐水和DMF灌胃。对比各组间踝关节肿胀程度、步态行为学评级,取大鼠踝关节滑膜组织病理切片苏木精-伊红染色,观察各组大鼠组织病理学改变及炎症细胞浸润情况,积分光密度法测定各组大鼠关节滑膜组织中消皮素D、NOD样受体蛋白3(NLRP3)及半胱氨酸天冬氨酸蛋白酶1(caspase-1)蛋白表达量。采用酶联免疫吸附试验法测定各组大鼠血清中的白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)。结果处置后4、8、24、48 h各时点MSU+DMF组和MSU组关节肿胀程度均大于生理盐水组,但MSU+DMF组均小于MSU组(均P<0.05)。处置后4、8、24、48 h各时点MSU+DMF组和MSU组大鼠步态行为学评级显著高于生理盐水组,但MSU+DMF组均低于MSU组(均P<0.05)。MSU组有大量炎性细胞浸润,炎症反应明显。MSU+DMF组与MSU组相比,组织病理炎症反应较轻,炎性细胞浸润较少,滑膜组织细胞分布较均匀。MSU组大鼠关节滑膜组织中NLRP3、caspase-1、消皮素D蛋白表达量及炎症因子IL-1β、IL-6、TNF-α水平均显著高于生理盐水组,MSU+DMF组以上指标均显著低于MSU组[炎症因子:(64±7)ng/L比(106±13)ng/L、(27±4)ng/L比(59±8)ng/L、(11.3±1.5)ng/L比(27.8±3.9)ng/L](均P<0.05)。结论DMF对MSU诱导大鼠急性痛风性关节炎具有保护作用,这可能和抑制NLRP3炎症小体及NLRP3炎症通路有关。Objective To investigate the protective effect of dimethyl fumarate(DMF)on acute gouty arthritis in rats and its mechanism.Methods Twenty-one male SD rats were randomly divided into physiological saline group,urate crystal(MSU)group,and MSU+DMF group after one week of feeding in an environment without specific pathogens,with seven rats in each group.In the physiological saline group,no model was made,and physiological saline was administered by gavage;The model of acute gouty arthritis was made by MSU in MSU group and MSU+DMF group,and the rats were gavaged with physiological saline and DMF respectively.The degree of ankle swelling and gait behavior rating were compared between the groups,and the pathological sections of rat ankle synovium were stained with hematoxylin-eosin.The histopathological changes and inflammatory cell infiltration of rats in each group were observed.The protein expressions of scutellarin D,NOD like receptor protein 3(NLRP3)and caspase-1 in synovial tissue of rats in each group were determined by integrated optical density method.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factorα(TNF-α)were determined by enzyme-linked immunosorbent assay.Results The joint swelling degrees of MSU+DMF group and MSU group were greater than those of normal saline group at 4,8,24 and 48 h after treatment,but the joint swelling degrees of MSU+DMF group were less than those of MSU group(all P<0.05).At 4,8,24,48 h after treatment,the MSU+DMF group and MSU group had significantly higher gait behavior rating than the physiological group,but the MSU+DMF group had significantly lower gait behavior rating than the MSU group(all P<0.05).The MSU group had a large number of inflammatory cell infiltration and obvious inflammatory response.Compared with the MSU group,the MSU+DMF group had less inflammatory response,less inflammatory cell infiltration,and more uniform distribution of synovial cells.The protein expression of NLRP3,caspase-1,and gasdermin D and the levels of IL-1β,IL-6,and TNF-αin

关 键 词：痛风性关节炎 NOD样受体蛋白3炎症小体 富马酸二甲酯 

分 类 号：R684.3[医药卫生—骨科学]