阿托伐他汀通过 AIM2 调控的裂解作用缓解老年性黄斑变性

IF 4.5 2区 医学 Q2 CELL BIOLOGY
Jing Lu, Yuxia He, Yong Du, Long Zhao, Ping Wu, Qinxin Shu, Hui Peng, Xing Wang
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引用次数: 0

摘要

老年性黄斑变性(AMD)的根本原因仍然难以捉摸,治疗方案也很有限,而阿托伐他汀(AT)有望改善AMD。我们的研究试图揭示引发AMD热蛋白沉积的具体机制,并阐明阿托伐他汀是否能通过抑制热蛋白沉积来改善Aβ1-40诱导的视网膜损伤。Aβ1-40诱发AMD动物模型,通过苏木精和伊红染色(H&E)、光学相干断层扫描(OCT)、视网膜电图(ERG)等方法评估AT的疗效。利用网络药理学和转录组学,我们确定了潜在的治疗途径。我们采用了 Western 印迹(WB)和定量实时 PCR(qPCR)方法来评估热昏迷的水平。体外视网膜色素上皮(RPE)细胞损伤系统由 Aβ1-40 引起,随后用 AT 或 JC2-11 处理。使用酶联免疫吸附测定法(ELISA)、免疫荧光染色法和白细胞分光光度法(WB)对热昏迷的程度进行量化。使用光学显微镜和扫描电子显微镜检查细胞形态变化。网络药理学和转录组学确定 AIM2/Caspase-1/GSDMD 为关键通路。AT改善了Aβ1-40造成的视网膜形态和功能损伤,并减少了AIM2、Asc、Caspase-1、GSDMD-N、Cleaved Caspase-1和细胞因子的产生,从而发挥了抗炎作用。此外,AT 还能改善 Aβ1-40 引起的 RPE 细胞膜破裂。JC2-11 的使用进一步证明,AT 可通过被 Aβ1-40 激活的 AIM2/Caspase-1/GSDMD 通路抑制 RPE 的脓毒症。这些发现阐明了 AT 通过有效阻碍热蜕变的进展而起到保护视网膜的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Atorvastatin Alleviates Age-Related Macular Degeneration via AIM2-Regulated Pyroptosis.

The underlying causes of age-related macular degeneration (AMD) remain elusive and treatment options of it are limited, while atorvastatin (AT) is expected to improve AMD. Our study sought to uncover the specific mechanisms that initiate pyroptosis in AMD and elucidate whether AT ameliorates Aβ1-40-induced retinal damage by inhibiting pyroptosis. An animal model of AMD was triggered by Aβ1-40, and the therapeutic efficacy of AT was evaluated by hematoxylin and eosin staining (H&E), Optical Coherence Tomography (OCT), Electroretinogram (ERG) and other methods. Utilizing network pharmacology in conjunction with transcriptomics, we identified potential therapeutic pathways. we employed Western blotting (WB) and quantitative real-time PCR (qPCR) methodologies to evaluate the levels of pyroptosis. In vitro system of retinal pigment epithelium (RPE) cells injury was caused by Aβ1-40 and subsequently treated with AT or JC2-11. The extent of pyroptosis was quantified using enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and WB. Cell morphological changes were examined using light microscopy and scanning electron microscopy. Network pharmacology and transcriptomics identified AIM2/Caspase-1/GSDMD as the key pathway. AT improved the retinal morphological and functional damage caused by Aβ1-40, and decreased the production of AIM2, Asc, Caspase-1, GSDMD-N, Cleaved Caspase-1 and cytokines to exert an anti-inflammatory effect. In addition, AT improved the ruptured membrane of RPE cells caused by Aβ1-40. The use of JC2-11 further demonstrated that AT inhibits pyroptosis of RPE via AIM2/Caspase-1/GSDMD pathway activated by Aβ1-40. These discoveries illuminate the retinal conservation role of AT by effectively hindering the progression of pyroptosis.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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