阿魏酸通过 Sirt1-NLRP3 通路降低辐射诱导的炎症反应

Yao Nie, Mingyue Huang, Tingyu Yang, Yu Mei, Huiting Zhang, Xue Wei, Yue Gao, Zengchun Ma
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引用次数: 0

摘要

通过辐射诱导炎症损伤模型,研究阿魏酸(FA)是否能通过Sirt1-NLRP3炎症通路减轻炎症反应。这将有助于发现辐射防护药物,并阐明辐射诱导炎症损伤的相关分子机制。 为了验证 FA 在体内的抗炎作用,我们建立了辐射诱导免疫炎症损伤的小鼠模型。将 C57BL/6J 小鼠随机分为六组,采用 5 Gy 全身照射进行建模。小鼠在照射前连续12天每天服用胃溶剂阿米福星或25、50或100 mg/kg FA。照射24小时后采集小鼠血清,观察炎症因子白细胞介素(IL)-1β、IL-18、IL-6和肿瘤坏死因子(TNF)-α的含量。对小鼠的脾脏和胸腺组织进行称重,并计算器官指数,用于病理检测和免疫荧光检测。 FA降低了辐射引起的脾脏和胸腺指数的下降。FA能明显减少血清中炎症因子的分泌,并逆转辐射引起的小鼠脾脏和胸腺淋巴细胞的减少。FA 激活了 Sirt1 并抑制了 NLRP3 炎性体的表达,从而减轻了炎症反应。 FA可能通过激活Sirt1和减少核苷酸寡聚化结构域(NOD)样受体热蛋白结构域相关蛋白3(NLRP3)炎性体的表达,从而减少炎性因子的分泌,减轻了辐射诱导的动物炎症反应。
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Ferulic Acid Reduces Inflammatory Response Induced by Radiation through Sirt1-NLRP3 Pathway
A model of inflammatory damage was induced by radiation to investigate whether ferulic acid (FA) can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway. This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage. A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo. C57BL/6J mice were randomly divided into six groups, and 5 Gy whole body irradiation was used for modeling. Mice were administered a gastric solvent, amifostine, or 25, 50, or 100 mg/kg FA daily for 12 d, consecutively, before irradiation. The serum of mice was collected 24 h after irradiation to observe the content of inflammatory factors interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection. FA reduced the radiation-induced decrease in the spleen and thymus indices. FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice. FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response. FA reduced radiation-induced inflammation in animals, possibly by activating Sirt1 and reducing nucleotide oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome expression, thereby reducing the secretion of inflammatory factors.
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