Association of zinc administration with growth suppression of intracranial aneurysms via induction of A20
Association of zinc administration with growth suppression of intracranial aneurysms via induction of A20
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DOI：
10.3171/2020.1.jns192047
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发表时间：
2021-03-01
影响因子：
4.1
通讯作者：
Miyamoto, Susumu
中科院分区：
文献类型：
--
作者：
Hayashi, Kosuke;Kataoka, Hiroharu;Miyamoto, Susumu
目的 锌是一种必需的微量营养素，具有多种生物效应，包括抗炎作用。此前，作者证明颅内动脉瘤（IAs）的发病机制与慢性炎症密切相关。在这项研究中，作者研究了施用锌是否会抑制大鼠模型中 IAs 的生长。 方法 作者分析了 Sprague-Dawley 雄性大鼠中手术诱导的 IAs，随后腹腔注射七水硫酸锌（ZnSO4；3 mg/kg/天）或载体治疗 4 周。 结果 在诱导后的两个治疗组和对照组中评估了实验诱导的 IAs 的大小和壁厚比。通过免疫组织化学和蛋白质印迹检查了锌在 IAs 中的作用。锌的施用显着抑制了动脉瘤的大小，并且还保留了内部弹性管腔。给予锌可显着减弱巨噬细胞对 IAs 的浸润。结论 锌治疗可显着增加大鼠 IAs 中抗炎信号蛋白 A20 的表达，A20 是核因子 kappa B (NF-kappa B) 通路的抑制剂。锌给药可以通过诱导 A20 引起的 NF-κ B 信号失活来防止大鼠 IAs 的生长。
OBJECTIVE Zinc is an essential micronutrient with multiple biological effects, including antiinflammation. Previously, the authors demonstrated that the pathogenesis of intracranial aneurysms (IAs) is strongly related to chronic inflammation. In this study, the authors investigated whether administration of zinc inhibits the growth of IAs in a rat model.METHODS The authors analyzed surgically induced IAs in Sprague-Dawley male rats, which were subsequently treated with intraperitoneal injections of zinc sulfate heptahydrate (ZnSO4; 3 mg/kg/day) or vehicle for 4 weeks.RESULTS Size and wall thickness ratios of experimentally induced IAs were assessed in both treatment groups after induction and in a control group. The effects of zinc administration in IAs were examined by immunohistochemistry and Western blotting. Zinc administration significantly suppressed aneurysm size and also preserved the internal elastic lumen. Administration of zinc significantly attenuated infiltration of macrophages into IAs.CONCLUSIONS Zinc treatment significantly increased expression of the antiinflammatory signaling protein A20, an inhibitor of the nuclear factor kappa B (NF-kappa B) pathway, in rat IAs. Zinc administration may prevent the growth of rat IAs by inducing A20-attributed inactivation of NF-kappa B signaling.