雷公藤红素通过NF-κB阻断尿酸钠晶体诱导的痛风性关节炎大鼠炎性分子表达  

Celastrol blocks inflammatory molecule expression through NF-κB in rats with monosodium urate monohydrate crystal-induced gout arthritis

作　　者：曹帆帆[1] 张登海[1] 杨哲军 王莹 徐莉敏[3] CAO Fanfan;ZHANG Denghai;YANG Zhejun;WANG Ying;XU Limin(Shanghai Key Lab of Artificial Intelligence(AI)-based Management of Inflammation and Chronic Diseases,Gongli Hospital of Shanghai Pudong New Area,Shanghai 200135,China;Clinical Laboratory,Shanghai Pudong Gaohang Community Health Service Center,Shanghai 201208,China;Clinical Laboratory,Gongli Hospital of Shanghai Pudong New Area,Shanghai 200135,China)

机构地区：[1]上海市浦东新区公利医院·上海市炎症与慢病管理人工智能重点实验室,上海200135 [2]上海市浦东新区高行社区卫生服务中心检验科,上海201208 [3]上海市浦东新区公利医院检验科,上海200135

出　　处：《同济大学学报（医学版）》2023年第2期173-179,共7页Journal of Tongji University(Medical Science)

基　　金：上海市浦东新区卫生系统学科带头人培养计划(PWRd2020-04);上海市浦东新区卫生科技面上项目(PW2020A-16);上海市浦东新区科技发展基金民生科研专项(PKJ2022-Y25)。

摘　　要：目的 观察雷公藤红素对急性痛风性关节炎大鼠的治疗作用及可能机制。方法 采用微晶型尿酸钠(monosodium urate monohydrate crystal, MSU)关节腔内注射诱导SD大鼠急性痛风性关节炎,同时用雷公藤红素(1 mg/kg)进行干预,测定关节肿胀度、关节浸出液中炎症因子、细胞因子的转录和蛋白水平,并进行病理学检查,同时观察雷公藤红素对关节滑膜和软骨组织NF-κB表达和活化的影响,并进行统计学分析。实验分为4组:对照组、雷公藤红素组、MSU诱导的模型组和雷公藤红素干预组(MSU+雷公藤红素),每组4只大鼠。结果 与对照组相比,尿酸钠晶体模型组大鼠踝关节明显肿胀,两组差异有统计学意义(P<0.01)。雷公藤红素干预组与模型组相比,没有观察到雷公藤红素对尿酸钠晶体导致的足肿胀有抑制作用(P>0.05)。雷公藤红素能抑制尿酸钠导致的模型鼠炎性介质IL-8、COX-2和NO的释放,并能抑制IL-8的mRNA转录。雷公藤红素能显著抑制尿酸钠导致的模型鼠关节滑膜和软骨组织的NF-κB表达和活化。结论 雷公藤红素在体内能抑制MSU导致的炎性介质IL-8、COX-2和NO的释放,这种抑制效果与其能抑制MSU导致的NF-κB表达和活化有关。雷公藤红素作为治疗急性痛风性关节炎的候选新药,值得进一步研究。Objective To investigate the effect and mechanism of celastrol on acute gouty arthritis in rats.Methods Acute gouty arthritis was induced by intraarticular injection of monosodium urate monohydrate crystal(MSU)in SD rats.The model rats were treated with celastrol(1 mg/kg)or DMSO by intraarticular injection in celastrol group and model group,respectively.The joint swelling degree,the transcription and protein levels of inflammatory factors and cytokines in the joint leachate were determined,and the histopathological examination was conducted.The effects of celastrol on the expression and activation of NF-κB in synovial membrane and cartilage tissues were observed.The experiment was divided into 4 groups with 4 rats in each group:control group(intraperitoneal injection of DMSO),celastrol group,MSU-induced model group and celastrol intervention group(MSU+celastrol).Results Compared with the control group,the ankle joint of rats in model group was significantly swollen(P<0.01).There was no significant difference in the degree of foot swelling between the celastrol group and model group(P>0.05).Celastrol inhibited the release of IL-8,COX-2 and NO and inhibited the expression of IL-8 mRNA in the joint leachate.Celastrol inhibited NF-κB expression and activation in synovial and cartilage tissues induced by MSU.Conclusion Celastrol can inhibit the release of inflammatory mediators IL-8,COX-2 and NO in the joint leachate,which is associated with the downregulation of NF-κB expression and activation in rats with MSU induced-acute gouty arthritis.

关 键 词：痛风性关节炎 雷公藤红素 炎性分子 核因子ΚB 

分 类 号：R961.1[医药卫生—药理学]