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橙黄决明素通过靶向啮齿动物模型中的NF-κB/NLRP3信号通路减轻干眼症

Aurantio-obtusin Alleviates Dry Eye Disease by Targeting NF-κB/NLRP3 Signaling in Rodent Models.

作者信息

Zhu Dan, Zheng Na, Deng Kebin, Li Liangchang

机构信息

Department of Ophthalmology, Hubei Provincial Hospital of Traditional Chinese Medicine, 430061, Wuhan, Hubei, China.

Department of Otolaryngology, Hubei Provincial Hospital of Traditional Chinese Medicine, 430061, Wuhan, Hubei, China.

出版信息

Biochem Genet. 2024 Apr;62(2):1-14. doi: 10.1007/s10528-023-10471-0. Epub 2023 Aug 26.

Abstract

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.

摘要

干眼疾病(DED)是一种常见的炎症性眼表疾病,严重影响患者的生活质量。橙钝叶决明素(AO)是从决明子中分离出的一种具有多种药理活性的生物活性蒽醌化合物。然而,AO在DED中的具体作用尚不清楚。在本研究中,通过苯扎氯铵(BAC)诱导建立了啮齿动物DED模型,随后局部应用AO。结果表明,局部应用AO可增加泪液分泌,减轻眼表损伤,并维持BAC诱导的DED大鼠杯状细胞数量(p<0.05)。酶联免疫吸附测定(ELISA)显示,AO治疗显著(p<0.001)降低了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。免疫组织化学染色和蛋白质免疫印迹法显示,AO治疗抑制了含NLR家族pyrin结构域3(NLRP3)炎性小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κB(NF-κB)信号通路的激活(p<0.001)。总之,AO治疗通过抑制NF-κB/NLRP3炎性小体信号通路减轻了BAC诱导的大鼠DED。

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