莫罗尼苷通过 NF-κB/MMPs 通路抑制类风湿滑膜细胞侵袭,从而减轻类风湿性关节炎的病情

IF 1.1 4区 医学 Q4 MEDICAL LABORATORY TECHNOLOGY
Yan Wang, Ruili Yin, Xin Li, Baoyu Zhang, Yuan Wang, Lijie Zhang, Yanan Cheng, Dong Zhao
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引用次数: 0

摘要

目的:莫罗尼苷(MOR)被报道可改善心脑血管疾病的炎症反应,但其对类风湿性关节炎(RA)的影响和机制仍不清楚。本研究旨在探讨吗罗尼甙对治疗类风湿性关节炎的有益作用,并探索吗罗尼甙对关节破坏的抗侵袭机制:方法:在体外(使用原代大鼠关节成纤维细胞样滑膜细胞(FLSs))使用伤口愈合试验检测原代大鼠FLSs的迁移。定量 RT-PCR 用于测量基质金属蛋白酶(MMP)MMP2 和 MMP9 的转录。用 Western 印迹法测定 MMP2、MMP9、p65、磷酸化-p65(p-p65)、核因子抑制剂(NF)-[式中:见正文]Bα(I[式中:见正文]Bα)、I[式中:见正文]B 激酶α/β(IKKα/β)和磷酸化-IKKα/β的表达。免疫荧光试验用于测量 p65 的核转位。在体内(使用胶原蛋白诱导的关节炎大鼠),通过常规苏木精和伊红检测关节组织病理学变化。免疫组化法测定 MMP2 和 MMP9 的表达:结果:莫罗尼苷可减少肿瘤坏死因子(TNF)α刺激的原代大鼠关节FLS的迁移。莫罗尼苷还能减轻胶原诱发关节炎(CIA)大鼠的RA-FLS侵入关节和关节破坏。进一步的分析表明,吗菌腈抑制了基质金属蛋白酶MMP2和MMP9在TNFα刺激的原代大鼠关节FLS和CIA大鼠关节中的过度表达。从机制上讲,吗菌腈抑制了I[式:见正文]B激酶α/β的活化,从而导致核因子(NF)-[式:见正文]B抑制剂水平的升高:本研究表明,吗罗尼西汀可通过抑制NF-[式:见正文]B/MMPs通路的活化,从而阻止FLSs的侵袭,防止关节破坏。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Morroniside Attenuates Rheumatoid Arthritis by Inhibiting Rheumatoid Synoviocytes Invasion through the NF-κB/MMPs Pathway.

Objective: Morroniside (MOR) has been reported to ameliorate inflammation in cardiovascular and cerebrovascular disease; however, its impact and mechanism on rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the beneficial role of morroniside in treating RA and explore the anti-invasive mechanism of morroniside on joint destruction.

Methods: In vitro (using primary rat articular fibroblast-like synoviocytes (FLSs)) a wound healing assay was used to detect the migration of primary rat FLSs. Quantitative RT-PCR was used to measure the transcription of matrix metalloproteinase (MMP) MMP2 and MMP9. Western blot was used to measure the expression of MMP2, MMP9, p65, phosphorylated-p65 (p-p65), inhibitor of nuclear factor (NF)-[Formula: see text]Bα (I[Formula: see text]Bα), I[Formula: see text]B kinase α/β (IKKα/β), and phosphorylated-IKKα/β. Immunofluorescence assay was used to measure the nuclear translocation of p65. In vivo (using rats with collagen-induced arthritis), the joint histopathological changes were detected by routine hematoxylin and eosin. Immunohistochemistry assay was used to measure the expression MMP2 and MMP9.

Results: Morroniside diminished tumor necrosis factor (TNF)α-stimulated migration of primary rat articular FLSs. Morroniside also attenuated RA-FLSs invasion into joint and joint destruction in rats with collagen-induced arthritis (CIA). Further analysis revealed that morroniside inhibited the overexpression of matrix metalloproteinase MMP2 and MMP9 in TNFα-stimulated primary rat articular FLSs and joints of CIA rats. Mechanistically, morroniside suppressed the activation of I[Formula: see text]B kinase α/β, which resulted in elevated levels of the inhibitor of nuclear factor (NF)-[Formula: see text]B.

Conclusion: The present study suggested that morroniside can prevent joint destruction by suppressing the activation of the NF-[Formula: see text]B/MMPs pathway, thereby preventing FLSs invasion.

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来源期刊
Annals of clinical and laboratory science
Annals of clinical and laboratory science 医学-医学实验技术
CiteScore
1.60
自引率
0.00%
发文量
112
审稿时长
6-12 weeks
期刊介绍: The Annals of Clinical & Laboratory Science welcomes manuscripts that report research in clinical science, including pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.
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