Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway.
Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway.
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瓜氨酸通过 Nrf2 信号通路抑制 ROS/NLRP3™ 依赖性细胞焦亡和细胞凋亡，从而防止 LPS™ 诱导的急性肺损伤
DOI：
10.3892/etm.2022.11569
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发表时间：
2022-10
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
--
作者：
急性肺损伤(ALI)是脓毒症患者常见的并发症，死亡率高。本研究旨在探讨有机化合物瓜氨酸对内毒素(LPS)诱导的ALI是否具有保护作用及其可能的机制。采用小鼠腹腔注射诱导ALI模型。注射内毒素(10 mg/kg)。瓜氨酸(1g/kg/d)ip。在注射脂多糖前7天。小鼠肺血管内皮细胞(MLVECs)分为5组：对照组、脂多糖、脂多糖+Cit、脂多糖+N-乙酰-L半胱氨酸组和脂多糖+Cit+ML385组。通过形态学改变判断肺损伤程度。免疫印迹分析和免疫荧光检测细胞凋亡和下垂情况。结果表明，瓜氨酸对ALI有明显的抑制作用。瓜氨酸预处理可减少NOD、LRR和PYRIN结构域蛋白3(NLRP3)炎性小体的表达，减少下垂和细胞凋亡。总活性氧(ROS)清除剂N-乙酰-L-半胱氨酸干预可减轻内毒素诱导的fl氨基转移酶相关的肾小球粘连和细胞凋亡。瓜氨酸预处理可抑制内毒素诱导的嗜酸性细胞死亡和凋亡。瓜氨酸减少细胞内ROS的积累并激活核因子红系2相关因子2(Nrf2)信号通路。此外，NRF2抑制剂ML385可逆转fl氨基转移酶介导的肾小球粘连中ROS的产生和NLRP3的生成，并抑制瓜氨酸诱导的细胞凋亡。综上所述，目前的数据表明，瓜氨酸可能通过抑制ROS/NLRP3依赖的炎性下垂和Nrf2信号通路而抑制细胞凋亡，从而对ALI起到保护作用。
Acute lung injury (ALI) is a common complication in patients with sepsis and is accompanied by high mortality. The present study aimed to investigate if the organic compound citrulline has a protective against lipopolysaccharide (LPS)-stimulated ALI and its potential mechanisms. ALI was induced in mice by intraperitoneal (i.p.) injection of LPS (10 mg/kg). Citrulline (1 g/kg/day) was administrated i.p. 7 days prior to LPS injection. Mouse lung vascular endothelial cells (MLVECs) were divided into five groups: Control, LPS, LPS + Cit, LPS + N-acetyl-L-cysteine (NAC) and LPS + Cit + ML385. Lung injury was determined by morphology changes. Apoptosis and pyroptosis were detected using western blot analysis and immunofluorescence. The present results indicated that citrulline can significantly attenuate ALI. Citrulline pretreatment decreased the expression of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and decreased pyroptosis and apoptosis. Intervention with the total reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine attenuated NLRP3 inflammasome-associated pyroptosis and apoptosis in LPS-treated MLVECs. Citrulline pretreatment inhibited pyroptotic cell death and apoptosis induced by LPS. Citrulline decreased accumulation of intracellular ROS and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Furthermore, the Nrf2 inhibitor ML385 reversed ROS generation, NLRP3 inflammasome-mediated pyroptosis and apoptosis suppressed by citrulline. In summary, the present data demonstrated that citrulline may confer protection against ALI via inhibition of ROS/NLRP3 inflammasome-dependent pyroptosis and apoptosis via the Nrf2 signaling pathway.
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