青藤碱抑制NLRP3和下游致炎因子表达改善佐剂性关节炎大鼠关节炎症状  

Sinoline inhibits NLRP3 and downstream inflammatory factors to alleviate the arthritis symptoms in adjuvant arthritis rats

作　　者：黄焱平 宋先兵[1] 杨珺[2] 汪陶荣 张晔 陈晓宇[3] 叶静[4] HUANG Yanping;SONG Xianbing;YANG Jun;WANG Taorong;ZHANG Ye;CHEN Xiaoyu;YE Jing(Department of Human Anatomy,Histology&Embryology,Anhui Medical College,Hefei 230601;Department of of Pathology,Anhui Medical College,Hefei 230601;Experimental Center for Morphology,Anhui Medical University,Hefei 230032;Department of Respiratory Medicine,The Second Affliated Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医学高等专科学校人体解剖与组织胚胎学教研室,安徽合肥230601 [2]安徽医学高等专科学校病理学教研室,安徽合肥230601 [3]安徽医科大学形态实验中心,安徽合肥230032 [4]安徽医科大学第二附属医院呼吸内科,安徽合肥230601

出　　处：《细胞与分子免疫学杂志》2023年第3期236-241,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：安徽省高校优秀青年人才支持计划项目(gxyq2019190);安徽高校自然科学研究重点项目(KJ2019A1100);国家自然科学基金(81373421);安徽医科大学基础与临床合作提升计划(2019xkjT027);安徽省自然科学基金(2108085MH264)。

摘　　要：目的探讨青藤碱对佐剂性关节炎(AA)大鼠的抗炎作用及含pyrin结构域核苷酸结合寡聚结构域样受体蛋白3(NLRP3)的变化。方法Wistar大鼠随机分为对照组、AA模型组、(100、200、400)mg/kg青藤碱组和100 mg/kg雷公藤组,每组10只。除对照组外,其余均采用Freund完全佐剂建立AA模型。建模后12 d,对照组和模型组给予等量生理盐水,其余各组分别灌胃给予相应药物,每天1次,连续16 d。通过多发性关节炎和关节肿胀度评价AA大鼠关节情况,Western blot法检测滑膜组织NLRP3蛋白水平,免疫组织化学染色法检测滑膜组织NLRP3表达和分布;ELISA检测大鼠血清白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)水平。结果与对照组比较,模型组多发性关节炎明显,关节肿胀度增加,青藤碱各治疗组和雷公藤组大鼠多发性关节炎和关节肿胀度明显降低;青藤碱各治疗组滑膜组织NLRP3蛋白表达减弱,血清中IL-1β、IL-6、TNF-α水平显著下降。结论青藤碱通过抑制NLRP3和下游致炎因子表达改善AA大鼠关节炎症。Objective To investigate the anti-inflammatory effects of sinoline on adjuvant arthritis(AA)rats and the changes of NOD like receptor pyrin-domain containing 3(NLRP3).Methods Wistar rats were randomly divided into control group,AA model group,(100,200,400)mg/kg sinomenine group and 100 mg/kg Tripterygium wilfordi group,with 10 rats in each group.Except for the control group,AA model was established by Freund complete adjuvant.12 days after modeling,control group and model group were given the same amount of normal saline,and other groups were given drugs by intragastric administration,once a day,for consecutive 16 days.Joint conditions of AA rats were evaluated by multiple arthritis and joint swelling.The level of NLRP3 protein in synovial tissues was detected by Western blot,and the expression and distribution of NLRP3 in synovial tissues were detected by immunohistochemical staining.Serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factorα(TNF-α)were detected by ELISA.Results Compared with the control group,multiple arthritis and joint swelling significantly increased in model group,while those significantly decreased in sinomenine treatment groups and Tripterygium wilfordi group.Decreased expression of NLRP3 protein in synovial tissue was observed,along with the significantly reduced levels of IL-1β,IL-6 and TNF-αin serum in sinoline treatment groups.ConclusionnSinolin can improve joint inflammation in AA rats by inhibiting NLRP3 and downstream inflammatory factors.

关 键 词：佐剂性关节炎(AA) 青藤碱 含pyrin结构域核苷酸结合寡聚结构域样受体蛋白3(NLRP3) 白细胞介素1β(IL-1β) IL-6 肿瘤坏死因子α(TNF-α) 

分 类 号：R285.5[医药卫生—中药学] R593.22[医药卫生—中医学] R332R684.3R364.5