Simvastatin attenuates delayed encephalopathy induced by carbon monoxide poisoning in rats by regulating oxidative stress, inflammation and NF-κB pathway
Simvastatin attenuates delayed encephalopathy induced by carbon monoxide poisoning in rats by regulating oxidative stress, inflammation and NF-κB pathway
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DOI：
10.1007/s13273-021-00124-x
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发表时间：
2021-02
影响因子：
1.7
通讯作者：
Z. Chu;Zuolong Liu;Wei Li;Dahai Xu;L. Pang
中科院分区：
文献类型：
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作者：
Z. Chu;Zuolong Liu;Wei Li;Dahai Xu;L. Pang
研究背景一氧化碳（CO）中毒是世界范围内发病和死亡的主要原因.迟发性脑病发生在中毒后一段时间内，患者未经有效治疗。辛伐他汀（Simvastatin，Sim）是一种降血脂药物，具有内皮保护作用和抑制炎症反应。本研究旨在探讨Sim对CO中毒迟发性脑病的影响。①采用2500 ppm CO气体染毒40 min，然后3000 ppm染毒30 min或直至意识丧失的方法建立急性CO中毒模型。治疗组给予Sim 20 mg/kg/d灌胃。行为学测试包括Morris水迷宫实验和穿梭箱实验。用H和E染色评价病理改变。用ELISA法检测炎性介质。结果Sim可减轻CO所致的大鼠行为学障碍，并可减轻海马神经细胞凋亡。SIM管理逆转了CO对氧化应激相关分子的影响。Sim还能抑制CO诱导的炎症介质的产生，CO暴露后eNOS水平降低，iNOS水平升高。Sim能显著抑制CO的作用，并能抑制NF-κB抑制蛋白IκBα的磷酸化，即抑制NF-κB α的磷酸化。结论辛伐他汀可通过调节氧化应激、炎症反应和NF-κB通路，减轻CO中毒后迟发性脑病的发生。
BackgroundCarbon monoxide (CO) poisoning is a leading cause of morbidity and mortality worldwide. The delayed encephalopathy occurs a period after poisoning in patients without effective treatment. Simvastatin (Sim), a lipid-lowering drug, was reported to exert endothelial protective effects and inhibit inflammatory response. This research focused on the effects of Sim on delayed encephalopathy caused by CO poisoning.ObjectiveThe acute CO poisoning model was established by exposing rats to 2500 ppm CO gas for 40 min, then 3000 ppm for 30 min or until they lost consciousness. Rats in the treatment group were given Sim (20 mg/kg/day, ig.). The behavioral tests included the Morris water maze test and shuttle box. The pathological changes were evaluated by H and E staining. The inflammatory mediators were analyzed by ELISA. The expression levels of eNOS, iNOS and the NF-κB-related proteins were analyzed by Western blot.ResultsThe results showed that Sim could alleviate CO-induced behavioral disorders and the hippocampal nerve cells apoptosis. Sim administration reversed the effects of CO on oxidative stress-related molecules. Sim could also inhibit the production of the inflammatory mediators induced by CO. The level of eNOS was decreased after CO exposure, while iNOS was increased. Sim could significantly inhibit the effects of CO. Furthermore, Sim inhibited the phosphorylation of IκBα (an NF-κB inhibitory protein), i.e., the activation of NF-κB, which indicated that Simvastatin reduced the inflammatory response induced by CO poisoning partially through inhibiting the activation of NF-κB signaling pathway.ConclusionTo sum up, our research indicated that Sim could attenuate the delayed encephalopathy induced by CO poisoning via regulating oxidative stress, inflammation and NF-κB pathway.