宣痹汤通过调控COX-2信号通路抑制大鼠急性痛风性关节炎炎症反应的机制研究  

Mechanism of Xuan Bi Decoction inhibiting acute gouty arthritis response in rats by regulating COX-2 signal pathway

作　　者：徐少晶 史家毓 徐子昱 熊丽辉 李欣 XU Shaojing;SHI Jiayu;XU Ziyu;XIONG Lihui;LI Xin(Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学临床医学院,长春130117

出　　处：《中国免疫学杂志》2024年第5期1069-1074,共6页Chinese Journal of Immunology

基　　金：吉林省卫生健康科技能力提升项目(2021JC066);吉林省教育厅科学技术研究项目(JJKH20220857KJ)。

摘　　要：目的:探究宣痹汤抑制环氧合酶-2(COX-2)通路对急性痛风性关节炎(GA)大鼠炎症的影响。方法:SD大鼠60只,随机分为对照组、模型组、塞来昔布组(20 mg/kg)、宣痹汤低剂量组(5 g/kg)、宣痹汤中剂量组(10 g/kg)、宣痹汤高剂量组(20 g/kg),每组10只。采用Coderre经典方法建立大鼠痛风模型,对各组大鼠一般情况进行观察,步态分析,评估关节肿胀程度;利用HE染色技术对大鼠踝关节滑膜组织进行观察;ELISA测定大鼠关节液中炎症因子IL-1β、TNF-α、PGE_(2)、LTB_(4)水平;免疫印迹法检测大鼠踝关节滑膜组织PGE受体2(EP2)和LTB受体1(BLT1)的表达情况;qRT-PCR测定COX-2、5-脂氧合酶(5-LOX)mRNA表达的影响。结果:模型组大鼠关节肿胀、跛足、毛发暗淡、精神萎靡;塞来昔布组、宣痹汤低、中、高剂量组的大鼠症状明显改善;相比于对照组,模型组大鼠步态评价、关节肿胀程度、组织病理学改变、IL-1β、TNF-α、PGE_(2)、LTB_(4)、COX-2、5-LOX、EP2、BLT1水平显著升高(P<0.05);与COX-2抑制剂塞来昔布组相比,宣痹汤(20 g/kg)在接受MSU晶体处理的大鼠中表现出更好的抗关节炎特性,同时伴有IL-1β、TNF-α、PGE_(2)、LTB_(4)、COX-2、5-LOX、EP2、BLT1表达的减少。结论:宣痹汤抑制GA大鼠中COX-2、5-LOX来改善MSU晶体诱导的炎症,并可能作为一种治疗GA新策略。Objective:The effect of Xuan Bi Decoction on inhibition of cyclooxygenase-2(COX-2)pathway on inflammation in rats with acute gouty arthritis(GA).Methods:Sixty SD rats randomly allocated into control group,model group,celecoxib group(20 mg/kg),Xuan Bi Decoction low-dose group(5 g/kg),Xuan Bi Decoction medium-dose group(10 g/kg),Xuan Bi Decoction highdose group(20 g/kg),with 10 rats in each group.The classic method of Coderre was used to establish a rat gout model and observe the general condition of each group of rats;analysis of rat gait scores and joint swelling of rats;the histopathological growth of rat ankle Synovial membrane were observed by HE staining;the levels of inflammatory factors IL-1β,TNF-α,PGE_(2)and LTB_(4)in rats joint fluid were detected by ELISA;Western blot detection of PGE_(2)receptor 2(EP2)and LTB receptor 1(BLT1)expressions in rats ankle synovial tissue;qRT-PCR to detect the effect of mRNA expression of COX-2 and 5-lipoxygenase(5-LOX).Results:Rats in the model group had swollen joints,lameness,lusterless fur and mental lethargy;the rats in the celecoxib group and Xuan Bi Decoction low,medium and high dose groups showed effective improvement in related symptoms;compared with control group,the gait score,degree of joint swelling,degree of histopathology,IL-1β,TNF-α,PGE_(2),LTB_(4),COX-2,5-LOX,EP2 and BLT1 levels of the rats in the model group were significantly higher(P<0.05);compared with the COX-2 inhibitor celecoxib,Xuan Bi Decoction(20 g/kg)showed better anti-arthritic properties in rats treated with MSU crystals,accompanied by reduced expression of IL-1β,TNF-α,PGE_(2),LTB_(4),COX-2,5-LOX,EP2 and BLT1.Conclusion:Dual inhibition of COX-2 and 5-LOX by Xuan Bi Decoction in GA rats to improve MSU crystal-induced inflammation and may serve as a novel therapeutic strategy.

关 键 词：宣痹汤 痛风性关节炎 COX-2 5-LOX 

分 类 号：R285.5[医药卫生—中药学]