首页|期刊导航|环境与职业医学|特定频率振动与血管内皮细胞铁死亡相关指标的关联性

特定频率振动与血管内皮细胞铁死亡相关指标的关联性OA

Association between specific-frequency vibration and ferroptosis-related indicators in vascular endothelial cells

中文摘要英文摘要

[背景]长时间振动暴露可导致血管内皮细胞功能障碍及细胞的损伤,振动与血管内皮细胞铁死亡的关联性研究尚不充分. [目的]探索职业振动暴露是否与手臂振动病(HAVD)患者血清中铁死亡相关标志物的改变相关,并通过体外细胞实验进一步探究振动暴露是否可能诱导血管内皮细胞发生铁死亡. [方法]①使用判断抽样方法,分别抽取患有 HAVD工人(HAVD组)、有职业振动暴露但未患HAVD工人(振动暴露组)及非手传振动作业工人(对照组)各 50例.分别使用血清铁测定试剂盒、丙二醛(MDA)检测试剂盒、超氧化物歧化酶(SOD)检测试剂盒检测三组工人体内血清铁、MDA、SOD含量的改变.分别使用单因素方差、二元 logistic回归分析三者与 HAVD的关联.②将人脐静脉内皮细胞(HUVEC)分为振动组以及对照组.振动组接受 120 Hz、6.5 m·s-2频段的振动,并且按振动时间分为 1 d 2 h、1 d 4 h、2 d 2 h、2 d 4 h四组;对照组除了不接触振动外,其他条件均与实验组相同.采用细胞亚铁比色法测试盒、还原型谷胱甘肽(GSH)比色法测试盒分别检测不同振动时间和频次对 HUVEC内亚铁离子(Fe2+)含量、GSH含量的影响.使用实时荧光定量聚合酶链反应(RT-qPCR)检测细胞铁死亡相关基因酰基辅酶 A合成酶长链家族成员 4(ACSL4)、肿瘤抑制蛋白 P53(P53)、重组人铁蛋白重链 1(FTH1)和谷胱甘肽过氧化酶 4(GPX4)mRNA的表达情况.使用蛋白免疫印迹检测 HUVEC铁死亡相关蛋白表达水平. [结果]①与对照组相比,HAVD组患者中血清铁、MDA含量均升高,SOD活性降低(均 P<0.05).logistic回归分析表明,血清铁水平升高与HAVD患病风险增加相关,OR(95%CI)=4.034(2.063~7.887);MDA水平升高亦与 HAVD风险增加相关,OR(95%CI)=1.523(1.026~1.936).②与对照组相比,振动 1 d 4 h和 2 d 4 h组细胞内 Fe2+含量增加,GSH含量降低(均 P<0.05).RT-qPCR结果显示:与对照组相比,振动 1 d 4 h和 2 d 4 h组 ACSL4和 P53的表达上调(均P<0.05);而各组振动内皮细胞 GPX4、FTH1 mRNA的表达均下调(均 P<0.05).蛋白免疫印迹结果显示:与对照组相比,振动 1 d 2 h和 1 d 4 h组 ACSL4、P53蛋白的表达水平上调(均P<0.05);振动1 d 4 h、2 d 2 h和2 d 4 h组FTH1、GPX4蛋白的表达水平下调(均P<0.05). [结论]职业性振动暴露与 HAVD工人体内铁代谢紊乱及氧化应激水平改变相关.体外研究进一步表明,振动刺激可导致血管内皮细胞铁蓄积、抗氧化能力下降,并诱导铁死亡相关分子表达失衡.本研究结果提示,铁死亡可能在振动相关血管损伤及HAVD发生中发挥一定作用.

[Background]Prolonged vibration exposure can lead to vascular endothelial cell dysfunction and cellular injury.However,research on the association between vibration and ferroptosis in vascular endothelial cells remains insufficient. [Objective]To explore whether occupational vibration exposure is associated with alterations in serum markers related to ferroptosis in patients with hand-arm vibration disease(HAVD),and to further investigate,through in vitro cell experiments,whether vibration exposure may induce ferroptosis in vascular endothelial cells. [Methods]①A judgmental sampling method was employed to select 50 workers with HAVD(the HAVD group),50 vibration-exposed workers without HAVD(the vibration exposure group),and 50 non-hand-transmitted vibration-exposed workers(the control group).Serum iron levels,malondialdehyde(MDA)content,and superoxide dismutase(SOD)levels were measured using serum iron assay kits,MDA detection kits,and SOD detection kits,respectively.One-way analysis of variance and binary logistic regression analysis were per-formed to examine the relationships between these indicators and HAVD.②Human umbilical vein endothelial cells(HUVEC)were divided into a vibration group and a control group.The vibration group was subjected to vibration at 120 Hz with an acceleration of 6.5 m·s-2 and further subdivided into four subgroups:1 d 2 h,1 d 4 h,2 d 2 h,and 2 d 4 h.The control group was treated identically except for vibration exposure.Cellular iron(Fe2+)content and reduced glutathione(GSH)levels in HUVEC were measured using ferrous iron colorimetric assay kits and GSH colorimetric assay kits,respectively,to assess the effects of different vibration exposure schedules.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to detect the mRNA expression levels of ferroptosis-related genes,including acyl-CoA synthetase long-chain family member 4(ACSL4),tumor suppressor protein P53(P53),ferritin heavy chain 1(FTH1),and glutathione peroxidase 4(GPX4).Western blot analysis was conducted to determine the protein expression levels of ferroptosis-related markers in HUVEC. [Results]①Compared with the control group,the patients in the HAVD group showed increased serum iron and MDA levels,along with decreased SOD levels(P<0.05).The logistic regression analysis indicated that elevated serum iron levels were significantly associated with an increased risk of HAVD(OR=4.034;95%CI:2.063,7.887),and elevated MDA levels were also associated with an increased risk of HAVD(OR=1.523;95%CI:1.026,1.936).②Compared with the control group,increased intracellular Fe2+content and decreased GSH content were observed in HUVECs in the 1 d 4 h and 2 d 4 h vibration subgroups(P<0.05).The RT-qPCR results showed that,compared with the control group,vibration exposures of 1 d 4 h and 2 d 4 h significantly upregulated the expression of ACSL4 and P53(P<0.05),whereas the mRNA expression levels of GPX4 and FTH1 were downregulated in all vibration-exposed endothelial cells(P<0.05).The Western blot results revealed that,compared with the control group,the vibration exposure schedules of 1 d 2 h and 1 d 4 h significantly upregulated the protein expression levels of ACSL4 and P53(P<0.05),while the vibration exposure schedules of 1 d 4 h,2 d 2 h,and 2 d 4 h significantly downregulated the protein expression levels of FTH1 and GPX4(P<0.05). [Conclusion]Occupational vibration exposure is associated with alterations in iron metabolism and oxidative stress status in workers with HAVD.The in vitro experiments further demonstrates that vibration stimulation induces intracellular iron accumulation and reduces antioxidant capacity in vascular endothelial cells,accompanied by dysregulated expression of ferroptosis-related molecules.These findings suggest that ferroptosis may play a role in vibration-induced vascular injury and the pathogenesis of HAVD.

吴思恒;杨虹雨;周堪寿;曾繁菲;陈青松;夏云

广东药科大学公共卫生学院,广东 广州 510224广东药科大学公共卫生学院,广东 广州 510224广东药科大学公共卫生学院,广东 广州 510224广东药科大学公共卫生学院,广东 广州 510224广东药科大学公共卫生学院,广东 广州 510224广东药科大学公共卫生学院,广东 广州 510224

医药卫生

血管内皮细胞振动手臂振动病铁死亡脂质过氧化

vascular endothelial cellvibrationhand-arm vibration diseaseferroptosislipid peroxidation

《环境与职业医学》 2026 (3)

278-285,8

国家自然科学基金项目(82204007)广东省基础与应用基础研究基金项目(2024A1515013049)

10.11836/JEOM25330

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