鸢尾素在实验性关节炎中的新作用:HMGB1/MCP1/壳三酸苷酶i介导的坏死性坏死的最新进展。

IF 5.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Redox Report Pub Date : 2022-12-01 DOI:10.1080/13510002.2022.2031516
Rowida Raafat Ibrahim, Noha M Shafik, Rasha Osama El-Esawy, Mervat H El-Sakaa, Heba M Arakeeb, Radwa Mahmoud El-Sharaby, Dina Adam Ali, Omnia Safwat El-Deeb, Sara Ragab Abd El-Khalik
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引用次数: 4

摘要

目的:坏死性坏死是一个紧密调节的炎性坏死性细胞死亡信号通路,参与类风湿关节炎(RA)等离散疾病的发病机制。鸢尾素是一种具有免疫调节作用的肌因子。鸢尾素作为一种新型药物通过调节免疫炎症、坏死分子和生化信号通路治疗实验性RA的疗效评价方法:30只雌性白化Wister大鼠单次皮下注射ⅱ型不完全弗氏佐剂胶原蛋白(CII-IFA), 10 d后再进行强化免疫。注射14天后,关节炎慢性期沉淀。15只大鼠每日注射鸢尾素,连续4周。量热法测定关节组织匀浆中RIPK-3、MLKL、HMGB1、MCP1、IL-6、CHIT1、MDA和PN的水平。采用qrt-PCR技术检测TNF-α mRNA表达水平。结果:结果显示,鸢尾素显著降低大鼠各组生化指标,除MDA显著高于未治疗组(ttt)。结论:鸢尾素通过调节实验性RA大鼠的免疫炎症、坏死分子和生化信号通路,具有治疗性抗炎和抗氧化作用。缩写:RA:类风湿关节炎;RIPK3:受体相互作用蛋白激酶1;MLKL:混合谱系激酶结构域样蛋白;HMGB1:高迁移率组蛋白盒1;MCP1:单核细胞趋化蛋白1;IL-6:白细胞介素6;CHIT1: Chitotriosidase;MDA:丙二醛;PN:过氧硝酸盐;TNF-α:肿瘤坏死因子;qrt-PCR:实时定量反转录PCR;CII-IFA: ii型胶原伴不完全弗氏佐剂;注:TNF-α基因(NCBI GenBank Nucleotide accession # NM_012675.3);家政基因GAPDH (NCBI GenBank Nucleotide accession # NM_017008.4)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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The emerging role of irisin in experimentally induced arthritis: a recent update involving HMGB1/MCP1/Chitotriosidase I-mediated necroptosis.

Objectives: Necroptosis is a tightly adjusted inflammatory necrotizing cell death signaling pathway that participates in pathogenesis of discrete diseases as rheumatoid arthritis (RA). Irisin is a myokine with immuno-modulatory effect. Evaluation of irisin efficiency as a novel therapeutic agent in experimentally induced RA via modulating immuno-inflammatory, necroptotic molecular and biochemical signaling pathways.

Methods: RA was induced in 30 female Wister albino rats by a single subcutaneous injection of collagen-II with incomplete Freund's adjuvant (CII-IFA) followed by booster immunization dose 10 days later. After 14 days of the injection, arthritis chronic phase was precipitated. 15 rats were treated by S.C irisin injection daily for 4 weeks. Joint tissue homogenate RIPK-3, MLKL, HMGB1, MCP1, IL-6, CHIT1, MDA, and PN levels were assessed calorimetrically. However, TNF-α mRNA expression level was evaluated by the qrt-PCR technique.

Results: The results showed that irisin significantly decreases the level of all assessed biochemical parameters, except MDA, which was significantly increased in comparison with the correspondent values in the arthritic group with no treatment (ttt).

Conclusions: Irisin exhibits therapeutic anti-inflammatory and antioxidant effects via modulating immuno-inflammatory, necroptotic molecular, and biochemical signaling pathways in experimentally induced RA in rats.

Abbreviations: RA: rheumatoid arthritis; RIPK3: receptor-interacting protein kinase 1; MLKL: mixed lineage kinase domain-like protein; HMGB1: High-mobility group protein box 1; MCP1: Monocyte chemoattractant protein 1; IL-6: Interleukin 6; CHIT1: Chitotriosidase; MDA: Malondialdehyde; PN: Peroxynitrite; TNF-α: Tumor Necrosis Factor; qrt-PCR: quantitative real-time reverse transcription PCR; CII-IFA: collagen-II with incomplete Freund's adjuvant; ttt: treatmentNote: TNF-α gene (NCBI GenBank Nucleotide accession # NM_012675.3); The housekeeping gene GAPDH (NCBI GenBank Nucleotide accession # NM_017008.4).

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来源期刊
Redox Report
Redox Report 生物-生化与分子生物学
CiteScore
6.10
自引率
0.00%
发文量
28
审稿时长
>12 weeks
期刊介绍: Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.
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