Article(id=1240929924559721181, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240929920461886112, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202403396, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1711036800000, receivedDateStr=2024-03-22, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773790349377, onlineDateStr=2026-03-18, pubDate=1717948800000, pubDateStr=2024-06-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773790349377, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773790349377, creator=13701087609, updateTime=1773790349377, updator=13701087609, issue=Issue{id=1240929920461886112, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='11', pageStart='1921', pageEnd='2112', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773790348400, creator=13701087609, updateTime=1773827281389, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241084828704109275, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240929920461886112, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241084828704109276, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240929920461886112, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2066, endPage=2071, ext={EN=ArticleExt(id=1240929925474079487, articleId=1240929924559721181, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Experimental study on copper death of mouse alveolar macrophages induced by nano-copper oxide, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the toxic effect of nano-copper oxide on copper death in mouse alveolar macrophages. Methods MTT assay was used to detect the survival rate of mouse alveolar macrophages (MH-S) treated with nano-copper oxide, transmission electron microscope to observe the morphology of MH-S cells, Western Blot to detect the expression of copper death protein FDX1 and DLAT, transcriptional group sequencing to explore the changes of cell gene expression and key signal pathways in the process of copper death induced by nano-copper oxide, and one-way ANOVA to analyze the difference. Results Copper oxide nanoparticles with 40nm size could enter MH-S cells, decrease the dose-response survival rate of MH-S cells (P < 0.001), increase the concentration of Cu²⁺ in MH-S cells, and induce the expression of FDX1 (P=0.004) and DLAT protein (P < 0.001). However, the administration of copper death inhibitor tetra thiomolybdate (TTM) reduced the cytotoxicity, decreased the level of intracellular Cu²⁺ (P=0.0038), and decreased the expression of FDX1 (P=0.012) and DLAT (P < 0.05).The sequencing results showed that nano-copper oxide could activate IL-17 inflammatory pathway, while TTM could inhibit IL-17 signal pathway. Conclusion Nano-copper oxide can induce the death of copper in mouse MH-S cells, which provides a new clue for the study of the toxic mechanism of nano-copper oxide.

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目的 探究纳米氧化铜诱导小鼠肺泡巨噬细胞铜死亡的毒性效应。方法 利用MTT实验检测纳米氧化铜处理小鼠肺泡巨噬细胞（MH-S）存活率；透射电镜观察MH-S细胞形态；Western Blot检测铜死亡蛋白FDX1与DLAT的表达水平；转录组测序探究纳米氧化铜诱导铜死亡过程中细胞基因表达变化与关键信号通路；单因素方差分析进行差异分析。结果 40 nm粒径的纳米氧化铜颗粒可以进入MH-S细胞内，引起MH-S细胞剂量-反应式的存活率下降（P<0.001），增加MH-S细胞内Cu²⁺浓度，诱导FDX1（P=0.004）与DLAT蛋白（P<0.001）表达水平上升；而施加铜死亡抑制剂四硫钼酸盐（TTM）干预后减轻了细胞毒性，降低了细胞内Cu²⁺水平（P=0.038），减少了铜死亡关键蛋白FDX1（P= 0.012）与DLAT（P<0.001）表达。测序结果表明纳米氧化铜具有激活IL-17炎症通路的作用，而施加TTM干预后抑制了IL-17信号通路。结论 纳米氧化铜具有诱导小鼠MH-S细胞铜死亡的毒性效应，为纳米氧化铜的毒作用机制研究提供了新线索。

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注：图A为纳米氧化铜及TTM干预对MH-S细胞存活率的影响；^*为相同浓度下两组的比较P<0.05；CuO为纳米氧化铜；图B为透射电镜下MH-S细胞内的纳米氧化铜颗粒，箭头表示纳米氧化铜颗粒，比例尺为5 μm。

, figureFileSmall=wnFya8QWZts3llmCDVQCiA==, figureFileBig=+SsOJrW+0dnKyaH8Nmwm6g==, tableContent=null), ArticleFig(id=1240929931329327316, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=EN, label=Figure 3, caption=Effects of CuO NPs and TTM intervention on intracellular copper ions in MH-S cells, figureFileSmall=BJ0ss/Lw1nUr3bnu6DiEMg==, figureFileBig=YIDrR3w8sSucqpnKCIO2Nw==, tableContent=null), ArticleFig(id=1240929931446767839, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=CN, label=图3, caption=纳米氧化铜及TTM干预对MH-S细胞内铜离子的影响, figureFileSmall=BJ0ss/Lw1nUr3bnu6DiEMg==, figureFileBig=YIDrR3w8sSucqpnKCIO2Nw==, tableContent=null), ArticleFig(id=1240929931564208364, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=EN, label=Figure 4, caption=CuO NPs increased the expression of FDX1 and DLAT in MH-S cells, figureFileSmall=CROtZ7tFkZSKnRJ/uXYCaQ==, figureFileBig=2MTU3qqrRY5CeCu/utNUMg==, tableContent=null), ArticleFig(id=1240929931652288756, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=CN, label=图4, caption=纳米氧化铜处理诱导MH-S细胞FDX1与DLAT蛋白表达上升, figureFileSmall=CROtZ7tFkZSKnRJ/uXYCaQ==, figureFileBig=2MTU3qqrRY5CeCu/utNUMg==, tableContent=null), ArticleFig(id=1240929931757146369, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=EN, label=Figure 5, caption=TTM decreased the expression of FDX1 and DLAT in CuO NPs-treated cells, figureFileSmall=0ghdlaUJxp4xqng9eog6Yw==, figureFileBig=BBeAVfSgu7+Blt9zaiHbUg==, tableContent=null), ArticleFig(id=1240929931849421065, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=CN, label=图5, caption=TTM降低纳米氧化铜处理后FDX1与DLAT蛋白表达, figureFileSmall=0ghdlaUJxp4xqng9eog6Yw==, figureFileBig=BBeAVfSgu7+Blt9zaiHbUg==, tableContent=null), ArticleFig(id=1240929931962667284, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=EN, label=Figure 6, caption=Transcriptome sequencing analysis of MH-S cells treated with CuO NPs and TTM, figureFileSmall=ldyyi+luskd9lneRrjPPQg==, figureFileBig=5eDI/TL94qbrwBJ6/L9s1Q==, tableContent=null), ArticleFig(id=1240929932080107807, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240929924559721181, language=CN, label=图6, caption=纳米氧化铜及TTM处理MH-S细胞后转录组测序分析

注：图A为纳米氧化铜处理MH-S细胞上调基因BP分析；图B为纳米氧化铜处理MH-S细胞上调基因KEGG分析；图C为TTM与纳米氧化铜共同处理MH-S细胞下调基因BP分析；图D为TTM与纳米氧化铜共同处理MH-S细胞下调基因KEGG分析。

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