阿司匹林触发的消退素D1对急性角膜炎大鼠非经典细胞焦亡的抑制作用
The inhibiting effect of Aspirin Triggered-Resolvin D1 in non-canonical pyroptosis in rats with acute keratitis.
作者信息
Wang Peng, Zhu Chengcheng, Liu Mingming, Yuan Ying, Ke Bilian
机构信息
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Tianjin Eye Hospital, Tianjin Eye Institute, Nankai University Affiliated Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
出版信息
Exp Eye Res. 2022 May;218:108938. doi: 10.1016/j.exer.2022.108938. Epub 2022 Feb 1.
PURPOSE
To investigate the effect of Aspirin Triggered-Resolvin D1 (AT-RvD1) as an anti-pyroptosis and anti-inflammatory agent on lipopolysaccharide (LPS) induced acute keratitis in Wistar rats.
METHODS
Acute keratitis in rats were induced by LPS stromal injection. Inflammatory reaction was measured by clinical score and histological observations. The non-canonical pyroptosis, the role of AT-RvD1 and Docosahexaenoic Acid (DHA) on non-canonical pyroptosis, were verified by quantification real-time PCR (qRT-PCR) and Western-blot. Besides, Human corneal epithelial cells (HCECs) primed with LPS, were stimulated with Nigericin, AT-RvD1 and necrosulfonamide (NSA), a Gasdermin-D (GSDMD) inhibitor separately. CCK-8 tests and flow cytometry were conducted to evaluate the cell viability and death ratio. And the marker of non-canonical pyroptosis were verified by Western blot.
RESULTS
AT-RvD1 and DHA both alleviated the inflammation of rat cornea through inhibiting the expression of Caspase-11 and p30 which was triggered by LPS. Meanwhile, the activation of Caspase-4 and p30 were also significantly suppressed by AT-RvD1 in vitro, which is consistent with the results in rats.
CONCLUSIONS
The non-canonical pyroptosis signaling pathways played an important role in rats with acute keratitis. In addition, AT-RvD1 can exert as an anti-inflammatory activity by inhibiting the non-canonical pyroptosis. Hence, it may be a promising and safe agent in treating acute keratitis.
目的
研究阿司匹林触发的消退素D1（AT-RvD1）作为一种抗细胞焦亡和抗炎剂对脂多糖（LPS）诱导的Wistar大鼠急性角膜炎的影响。
方法
通过LPS基质注射诱导大鼠急性角膜炎。通过临床评分和组织学观察来测量炎症反应。通过定量实时PCR（qRT-PCR）和蛋白质免疫印迹法验证非经典细胞焦亡、AT-RvD1和二十二碳六烯酸（DHA）对非经典细胞焦亡的作用。此外，用LPS预处理的人角膜上皮细胞（HCECs）分别用尼日利亚菌素、AT-RvD1和坏死磺酰胺（NSA，一种Gasdermin-D（GSDMD）抑制剂）刺激。进行CCK-8试验和流式细胞术以评估细胞活力和死亡率。并通过蛋白质免疫印迹法验证非经典细胞焦亡的标志物。
结果
AT-RvD1和DHA均通过抑制LPS触发的Caspase-11和p30的表达减轻大鼠角膜炎症。同时，在体外，AT-RvD1也显著抑制了Caspase-4和p30的激活，这与在大鼠中的结果一致。
结论
非经典细胞焦亡信号通路在急性角膜炎大鼠中起重要作用。此外，AT-RvD1可通过抑制非经典细胞焦亡发挥抗炎活性。因此，它可能是治疗急性角膜炎的一种有前景且安全的药物。
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