[1]刘 玉,朱德强,高 薇.白花丹素对人类风湿关节炎成纤维样滑膜细胞凋亡的影响[J].中国药理学通报,2018,(08):1126-1133.[doi:10.3969/j.issn.1001-1978.2018.08.019]
 LIU Yu,ZHU De-qiang,GAO Wei.Effects of plumbagin on proliferation and apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis[J].Chinese Pharmacological Bulletin,2018,(08):1126-1133.[doi:10.3969/j.issn.1001-1978.2018.08.019]
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白花丹素对人类风湿关节炎成纤维样滑膜细胞凋亡的影响()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1126-1133
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
Effects of plumbagin on proliferation and apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
文章编号:
1001-1978(2018)08-1126-08
作者:
刘 玉1朱德强2高 薇1
锦州医科大学1.附属第一医院风湿免疫科、2.基础医学院病理与病理生理教研室,辽宁 锦州 121000
Author(s):
LIU Yu1ZHU De-qiang2GAO Wei1
1.Dept of Rheumatology and Immunology,the First Affiliated Hospital; 2.Dept of Pathology and Pathophysiology,School of Basic Medicine, Jinzhou Medical University,Jinzhou Liaoning 121000,China
关键词:
白花丹素 成纤维样滑膜细胞 类风湿关节炎 凋亡 JAK2/STAT3信号通路 增殖
Keywords:
plumbagin fibroblast-like synoviocytes rheumatoid arthritis apoptosis JAK2/STAT3 signaling pathway proliferation
分类号:
R284.1; R322.72,R329.24; R329.25; R593.220.22
DOI:
10.3969/j.issn.1001-1978.2018.08.019
文献标志码:
A
摘要:
目的 探究白花丹素(plumbagin,PLB)对体外培养的人类风湿关节炎(RA)成纤维样滑膜细胞(FLSs)增殖和凋亡的作用,并探讨其可能的作用机制。方法 体外分离并传代培养RA FLSs,MTT与集落形成实验检测PLB对RA FLSs活力及增殖的影响; ELISA法检测FLSs炎症介质TNF-α、IL-6的分泌水平; Hoechst 33342染色法、FCM实验检测RA FLSs的凋亡情况; Western blot检测PLB对RA FLSs中Bcl-2、Bax、cleaved caspase-3、p-JAK2、p-STAT3蛋白表达的影响。结果 LPS诱导后,PLB对FLSs的增殖率呈现浓度依赖的抑制效应(P<0.05)。LPS+PLB组及LPS+MTX组与模型组相比,炎症因子分泌量下降(P<0.05),细胞凋亡率明显增加(P<0.05)。Western blot结果显示,与模型组比较,LPS+PLB组及LPS+MTX组促凋亡蛋白Bax、cleaved caspase-3表达升高(P<0.05),抗凋亡蛋白Bcl-2及通路蛋白p-JAK2、p-STAT3表达降低(P<0.05)。结论 PLB能降低RA FLSs增殖活力并诱导其凋亡,可能与其降低JAK2及STAT3的磷酸化程度,进而影响FLSs的凋亡途径有关。
Abstract:
Aim To evaluate the proliferation and apoptosis effects of different doses of plumbagin(PLB)on LPS-stimulated human rheumatoid fibroblast-like synoviocytes(FLSs)and explore the underlying mechanism.Methods FLSs were isolated from primary syn-ovial tissues obtained from rheumatoid arthritis(RA) patients.Cell viability and proliferation were measured with MTT and colony formation test.The pro-inflammatory cytokines were assessed using ELISA assay.The cell apoptosis was detected by flow cytometry and Hoechst 33342 staining.The protein expression levels of Bcl-2,Bax,cleaved caspase-3,p-JAK2 and p-STAT3 were detected with Western blot.Results Compared with model group,PLB dose-dependently inhibited LPS-induced cell proliferation ability of human RA FLSs in vitro (P<0.05).Flow cytometry and Hoechst 33342 staining showed that PLB and MTX significantly promoted apoptotic cell percentage in LPS-stimulated RA FLSs(P<0.05).ELISA showed that the LPS-stimulated production of TNF-α and IL-6 decreased after PLB and MTX intervention compared with model group(P<0.01).After treatment with PLB(0.5,3 μmol·L-1)and MTX(1.0 mg·L-1)in RA FLSs,the protein expression levels of Bax and cleaved caspase-3 obviously increased( P<0.05 ),meanwhile,the expression levels of Bcl-2,p-JAK2 and p-STAT3 markedly decreased(P<0.05).Conclusion PLB inhibits the growth and promotes the apoptosis of RA FLSs,which may be attributable to its down-regulation of JAK2 and STAT3 phosphorylation,and in turn its influence on apoptotic pathway of FLSs.

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备注/Memo

备注/Memo:
收稿日期:2018-04-15,修回日期:2018-05-16
基金项目:辽宁省自然科学基金资助项目(No 30302150106)
作者简介:刘 玉(1990-),女,硕士生,研究方向:中药单体治疗类风湿关节炎,E-mail:18840107209@163.com;
高 薇(1968-),女,博士,教授,主任医师,硕士生导师,研究方向:类风湿关节炎发病机制及治疗,通讯作者,E-mail:gaowei6678@126.com
更新日期/Last Update: 2018-07-26