摘要
目的探讨桔梗总皂苷(CKS)对佐剂性关节炎(AA)大鼠的作用及部分机制研究。方法 60只SD大鼠随机分为6组,每组10只,分别为正常组、模型组、CKS低、中、高剂量组(50、100、200 mg/kg)及阳性药来氟米特组(2 mg/kg)。采用弗氏完全佐剂注射左后足趾皮内建立AA大鼠模型,观察各组大鼠足肿胀度、多发性关节炎指数并进行组织病理学检查;ELISA试剂盒检测血清中肿瘤坏死因子-α(TNF-α)和白介素1β(IL-1β)的水平;Real-time PCR和Western blot法检测各组大鼠滑膜组织中葡萄糖调节蛋白78(GRP78)、X盒结合蛋白1(XBP1)、CCAAT增强子结合蛋白同源蛋白(CHOP)、TNF-αm RNA和蛋白表达的情况。结果 CKS(100、200 mg/kg)可显著抑制大鼠继发性足肿胀并减轻其膝关节的病理变化;可将大鼠血清中TNF-α和IL-1β的水平明显降低(P<0.05);同时可以下调GRP78、XBP1、CHOP、TNF-αm RNA和蛋白的表达(P<0.05)。结论 CKS对AA大鼠具有一定的治疗作用,其机制可能是与抑制内质网应激GRP78/XBP1/CHOP信号通路,从而抑制滑膜细胞分泌和表达的TNF-α有关。
Objective To explore the effect of Platcodon grandiflorum total saponins (CKS) in adjuvant-induced arthritis (AA) rats and its possible mechanisms. Methods Sixty SD rats were randomly divided into six groups: normal group, model group, CKS(50 mg/kg), CKS(100 mg/kg), CKS(200 mg/kg) group and leflunomide (2 mg/kg) group. AA animal model was induced by complete Freund' s adjuvant toothed, then the paw swelling, pol- yarthritis index and histopathological changes were observed. Tumor necrosis factor-α(TNF-α) and interleukin 1 β (IL-1 β) from blood serum were detected by ELISA. The mRNA and protein expressions of 78-KD glucose regula- ted protein ( GRP78 ), X-box binding protein 1 ( XBP1 ), CCAAT/enhancer binding protein homologous (CHOP) and TNF-α were evaluated by real-time PCR and Western blot assay. Results In vivo, our data showed that CKS (100,200 mg/kg) could obviously suppress the secondary paw swelling, improve the morphologic changes of artic- ular cartilages and synovium, and decrease TNF-α and IL-1 β serum levels (P 〈 0. 05). The real-time PCR and Western blot resuhs displayed that CKS could significantly inhibit GRP78, XBP1, CHOP and TNF-α expressions in AA group (P 〈 0. 05 ). Conclusion This study indicates that CKS could improve the adjuvant-induced arthritis in a dose-dependent manner. The inhibition of GRP78/XBP1/CHOP/TNF-α signaling pathways is involved in CKS- mediated modulation of inflammation.
作者
陈昭琳
李俊
马陶陶
黄成
沈爱宗
唐丽琴
张善堂
朱鹏里
Chen Zhaolin1 , Li Jun2,3,4, Ma Taotao2,3,4, et al(1Dept of Pharmacy, The Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001 ; 2School of Pharmacy,Anhui Medical University, Hefei 230032 ;3Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei 230032 ;4Anhui Institute of Innovative Drugs, Hefei 23003)
出处
《安徽医科大学学报》
CAS
北大核心
2018年第3期395-400,共6页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81473268
81602344)
安徽省高校自然科学基金(编号:KJ2016A365)
关键词
桔梗总皂苷
佐剂性关节炎
TNF-α
内质网应激
Platcodon grandiflorum total saponins
adjuvant arthritis
TNF-α
endoplasmic reticulum stress