硫氧还蛋白-1 通过抑制 NLRP3 炎性小体减轻动脉粥样硬化发展。
Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome.
机构信息
Department of Cardiology, Yiwu Central Hospital, 519 Nanmen Street, Yiwu, 322000, Zhejiang, China.
出版信息
Endocrine. 2020 Oct;70(1):65-70. doi: 10.1007/s12020-020-02389-z. Epub 2020 Jun 30.
BACKGROUNDS
The thioredoxin-1 has atheroprotective effects via regulating oxidative stress and inflammation. In addition, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome also contributes to atherosclerosis development. However, whether the thioredoxin-1 suppresses atherosclerosis development by modulating the NLRP3 inflammasome remains unclear.
METHODS
The regulation of NLRP3 inflammasome by thioredoxin-1 was determined in vitro on macrophage cells after ox-LDL (oxidized low-density lipoprotein) stimulation. The IL-1β and caspase-1 p10 secretion were assessed by ELISA and western blot. Finally, the thioredoxin-1/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice.
RESULTS
Thioredoxin-1 suppressed the expression of NLRP3, the secretion of IL-1β and caspase-1 p10 in vitro. And ROS stimulation activated the NLRP3 inflammasome which was inhibited by thioredoxin-1. In the mouse model of atherosclerosis, thioredoxin-1 delivered by lentivirus vector inhibited atherosclerosis development. And the atheroprotective effects of thioredoxin-1 were attenuated by ROS stimulation. Furthermore, the regulation of NLRP3 inflammasome by thioredoxin-1 was also confirmed in vivo.
CONCLUSIONS
We demonstrated here that the thioredoxin-1 had atheroprotective functions through thioredoxin-1/NLRP3 inflammasome pathway.
背景
硫氧还蛋白-1 通过调节氧化应激和炎症具有抗动脉粥样硬化作用。此外，NLR 家族 pyrin 结构域包含 3（NLRP3）炎性小体也有助于动脉粥样硬化的发展。然而，硫氧还蛋白-1 是否通过调节 NLRP3 炎性小体来抑制动脉粥样硬化的发展尚不清楚。
方法
用 ox-LDL（氧化低密度脂蛋白）刺激巨噬细胞细胞后，在体外确定硫氧还蛋白-1 对 NLRP3 炎性小体的调节作用。通过 ELISA 和 Western blot 测定 IL-1β 和 caspase-1 p10 的分泌。最后，在载脂蛋白 E 缺陷小鼠中证实了硫氧还蛋白-1/NLRP3 炎性小体途径。
结果
硫氧还蛋白-1 抑制了 NLRP3 的表达、IL-1β 和 caspase-1 p10 的体外分泌。ROS 刺激激活了 NLRP3 炎性小体，而硫氧还蛋白-1 抑制了 NLRP3 炎性小体。在动脉粥样硬化小鼠模型中，通过慢病毒载体递送的硫氧还蛋白-1 抑制了动脉粥样硬化的发展。ROS 刺激减弱了硫氧还蛋白-1 的抗动脉粥样硬化作用。此外，还在体内证实了硫氧还蛋白-1 对 NLRP3 炎性小体的调节作用。
结论
我们在这里证明，硫氧还蛋白-1 通过硫氧还蛋白-1/NLRP3 炎性小体途径具有抗动脉粥样硬化作用。
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