通过靶向 NF-κB/NLRP3 信号在啮齿动物模型中缓解干眼症

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-04-01 Epub Date: 2023-08-26 DOI:10.1007/s10528-023-10471-0
Dan Zhu, Na Zheng, Kebin Deng, Liangchang Li
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引用次数: 0

摘要

干眼症(DED)是一种常见的眼表炎症性疾病,严重影响患者的生活质量。金合欢素(AO)是从决明子中分离出来的一种生物活性蒽醌化合物,具有多种药理活性。然而,AO 在 DED 中的具体功能尚未明确。本研究通过苯扎氯铵(BAC)诱导建立了啮齿类 DED 模型,然后局部施用 AO。结果表明,在 BAC 诱导的 DED 大鼠中,局部施用 AO 增加了泪液分泌,减轻了眼表破坏,并保持了鹅口疮细胞的数量(p˂0.05)。酶联免疫吸附试验(ELISA)显示,AO 治疗显著减少了 BAC 诱导的 DED 大鼠结膜和角膜中促炎细胞因子和趋化因子的产生(p˂0.001)。免疫组化染色和 Western 印迹显示,AO 治疗抑制了 NLR 家族含吡咯啉结构域 3(NLRP3)炎性体相关蛋白的表达水平,并抑制了大鼠结膜和角膜中核因子卡巴 B(NF-κB)信号通路的激活(p˂0.001)。总之,通过抑制 NF-κB/NLRP3 炎性体信号通路,AO 治疗可减轻 BAC 诱导的大鼠 DED。
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Aurantio-obtusin Alleviates Dry Eye Disease by Targeting NF-κB/NLRP3 Signaling in Rodent Models.

Dry eye disease (DED) is a common inflammatory ocular surface disorder, seriously affecting the quality of life of patients. Aurantio-obtusin (AO) is a bioactive anthraquinone compound isolated from Semen Cassiae which has multiple pharmacological activities. Nonetheless, the specific function of AO in DED is unclarified. In this study, a rodent DED model was established by benzalkonium chloride (BAC) induction, followed by topical administration of AO. The results showed that topical application of AO increased tear production, mitigated ocular surface disruption and maintained the number of goblet cells in BAC-induced DED rats (p˂0.05). ELISA revealed that AO treatment significantly (p˂0.001) reduced the production of proinflammatory cytokines and chemokines in the conjunctiva and cornea of BAC-induced DED rats. Immunohistochemical staining and western blotting showed that AO treatment suppressed the expression levels of NLR family pyrin domain containing 3 (NLRP3) inflammasome-related proteins, and inhibited activation of nuclear factor kappa B (NF-κB) signaling pathway in rat conjunctiva and cornea (p˂0.001). In conclusion, AO treatment alleviates BAC-induced DED in rats by inhibiting NF-κB/NLRP3 inflammasome signaling pathway.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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