NaF暴露經鈣內流和p38 MAPK/RIPK1介導紅細胞衰亡
首發時間:2025-11-10
高大學(1997-),男,貴州民族大學2023級環境工程碩士研究生,主要研究方向:環境毒理學
李文清 1 畢文澤 1 郭明珠 1 徐放 1 劉靜 1劉靜(1987-),女,副教授,碩導,主要研究方向:環境毒理學
摘要:目的: 探索氟對紅細胞的損傷及毒性機理。 方法: 將外周血紅細胞暴露于0、10、25、50和100 μM的氟化鈉(NaF)中,觀察并分析NaF暴露對紅細胞的損傷表現及毒性機理。首先,通過檢測細胞溶血、乳酸脫氫酶(LDH)釋放、磷脂酰絲氨酸(PS)外翻、細胞數目和形態評估NaF對細胞的毒性效應;其次,通過氧化應激、鈣離子(Ca2+)遷移和各凋亡通路探索其毒性機理。 結果:與對照組相比,紅細胞暴露于不同劑量的NaF 6 h后,引起紅細胞溶血、膜通透性增加、細胞數目減少和細胞形態異常等現象;進一步的研究發現,NaF暴露促進了紅細胞內Ca2+和活性氧(ROS)水平的增加;隨后,通過清除胞內Ca2+和ROS觀察到NaF暴露通過Ca2+內流介導了磷脂酰絲氨酸(PS)外翻,且ROS的上調對此也有一定貢獻;最后,通過阻斷劑干擾實驗發現,p38 MAPK和RIPK1的激活也參與了NaF暴露引起的紅細胞PS外翻現象。 結論:NaF暴露誘導了紅細胞的衰亡,主要表現為紅細胞溶血、膜透性增加、PS外翻和細胞形態異常等,進一步機理探索認為是胞內Ca2+內流和p38 MAPK與RIPK1信號通路的激活介導了NaF引起的紅細胞毒性。 該研究為過量氟攝取引起健康風險的預防和安全性評估提供了理論基礎。
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NaF Exposure Promotes Eryptosis via Calcium Influx and p38 MAPK/RIPK1 Activation
高大學(1997-),男,貴州民族大學2023級環境工程碩士研究生,主要研究方向:環境毒理學
Li Wenqing 1 Bi Wenze 1 Guo Mingzhu 1 Xu Fang 1 Liu Jing 1劉靜(1987-),女,副教授,碩導,主要研究方向:環境毒理學
Abstract:In order to explore the damage and toxic mechanism of fluorine on erythrocytes, in current study, peripheral erythrocytes were exposed to 0, 10, 25, 50 and 100 μM sodium fluoride (NaF), then explored its toxic phenotype and mechanism. First of all, to evaluate its effects on erythrocytes, hemolysis, lactic dehydrogenase (LDH) release, phosphatidylserine (PS) exposure, the changes of cell numbers and shape were detected.Next, to assess its toxic mechanism, oxidative stress, calcium mobilization and different apoptotic pathways were monitored。 The results indicated that, different dosage of NaF increased cell hemolysis, membrane permeability, decreased cell number and changed cell shape on erythrocytes; additionally, NaF exposure promoted calcium influx and cellular reactive oxygen species (ROS) levels;further study by calcium and ROS depletion confirmed that NaF activated calcium influx mediated in PS translocation, and these calcium influx and PS exposure were also associated to ROS increasing; ultimately, the blocking of different apoptotic pathways revealed that p38 MAPK and RIPK1 were involved in NaF induced PS translocation. Overall, this study provides a theoretical basis for health risk prevention and assessment caused by excessive fluorine intake .
Keywords: Sodium fluoride Red blood cells Eryptosis Calcium ion
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NaF暴露經鈣內流和p38 MAPK/RIPK1介導紅細胞衰亡
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