Article(id=1211269162010284312, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.04.03, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1610640000000, receivedDateStr=2021-01-15, revisedDate=1614614400000, revisedDateStr=2021-03-02, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718672515, onlineDateStr=2025-12-26, pubDate=1619539200000, pubDateStr=2021-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718672515, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718672515, creator=13701087609, updateTime=1766718672515, updator=13701087609, issue=Issue{id=1211269157790806494, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='4', pageStart='319', pageEnd='424', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718671510, creator=13701087609, updateTime=1766718756000, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269512217882745, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269512217882746, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=333, endPage=339, ext={EN=ArticleExt(id=1211269162933031230, articleId=1211269162010284312, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Effect and mechanism of artemisinin on alleviating vascular endothelial cell injury induced by oxidized low density lipoprotein, columnId=1190310110212751762, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Basic Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the effects of artemisinin (ART) on vascular endothelial cell injury induced by oxidized low density lipoprotein (ox-LDL), and explore its potential molecule mechanism. Methods The human umbilical vein endothelial cells EA.hy926 in logarithmic phase were treated respectively with 0, 50, 100, 150 and 200 mg/ml of ox-LDL and 0, 1,5, 10 and 20 mmol/L of ART. The cell viability were detected by MTT assay. To detected the effect of ART on cells, the EA.hy926 cells were divided into control group (without any treatment), ox-LDL group (treated with 100 mg/ml ox-LDL), ox-LDL+ART group (treated with 100 mg/ml ox-LDL and 10 mmol/L ART) and ox-LDL+ART+3-methyladenine (3-MA) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 5 mmol/L 3-MA). To detected the effect of transient receptor potential channel vanillic acid receptor subtype Ⅳ (TRPV4) on the cells, the EA.hy926 cells were divided into control group, ox-LDL group, ox-LDL+ART group and ox-LDL+ART+ruthenium red (RR) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 10 mmol/L RR). The cell viability were detected by MTT assay. The expressions of TRPV4, autophagy associated proteins (LC3-Ⅱ/LC3-Ⅰ and p62)and apoptosis associated protein (Bcl-2, Bax) were detected by Western blotting. Cell apoptosis were detected by flow cytometry. Results The cell viability of EA.hy926 decreased with the increase of ox-LDL concentration. The viability of ox-LDL induced cells was significantly upregulated by ART (P<0.05). Compared with the control group, the viability of cells, and the expression levels of p62, Bcl-2 and TRPV4 decreased significantly in the ox-LDL group (P<0.05), but the LC3-Ⅱ/LC3-Ⅰ ratio, cell apoptosis rate and expression level of Bax was significantly up-regulated in ox-LDL group (P<0.05). Compared with the ox-LDL group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, the protein expression levels of Bcl-2 and TRPV4 increased significantly, but the cell apoptosis rate, protein expression levels of p62 and Bax decreased significantly in ox-LDL+ART group (P<0.05). Compared with the ox-LDL+ART group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, and protein expression level of Bcl-2 decreased significantly (P<0.05), but the cell apoptosis rate, protein expression levels of p62 and Bax were up-regulated significantly in ox-LDL+ART+3-MA group and ox-LDL+ART+RR group (P<0.05). Conclusion ART can promote autophagy by activating TRPV4 to reduce ox-LDL induced vascular endothelial cell injury.

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目的 探讨青蒿素(ART)对氧化低密度脂蛋白(ox-LDL)诱导的血管内皮细胞损伤的作用及其潜在的分子机制。方法 分别用0、50、100、150、200 mg/ml的ox-LDL及0、1、5、10、20 mmol/L的ART处理对数生长期的人脐静脉内皮细胞EA.hy926，采用MTT法检测细胞活性。为检测ART对细胞的影响，将EA.hy926细胞分为4组：对照组(无处理)、ox-LDL组(100 mg/ml ox-LDL)、ox-LDL+ART组(100 mg/ml ox-LDL+10 mmol/L ART)及ox-LDL+ART+3-甲基腺嘌呤(3-MA)组(100 mg/ml ox-LDL+10 mmol/L ART+5 mmol/L 3-MA)；为检测瞬时感受器电位通道香草酸受体亚型Ⅳ(TRPV4)对细胞的影响，将EA.hy926细胞分为4组：对照组、ox-LDL组、ox-LDL+ART组及ox-LDL+ART+钌红(RR)组(100 mg/ml ox-LDL+10 mmol/L ART+10 mmol/L RR)。采用MTT法检测细胞活性，Western blotting检测TRPV4、自噬相关蛋白(LC3-Ⅱ/LC3-Ⅰ、p62)及凋亡相关蛋白(Bcl-2、Bax)的表达，流式细胞仪检测细胞凋亡情况。结果 EA.hy926细胞活性随着ox-LDL浓度的升高而降低，而ART作用于ox-LDL诱导的细胞后，细胞活性明显升高(P<0.05)。与对照组比较，ox-LDL组细胞活性，p62、Bcl-2、TRPV4表达水平明显降低，而LC3-Ⅱ/LC3-Ⅰ比值、细胞凋亡率、Bax表达水平明显升高，差异均有统计学意义(P<0.05)。与ox-LDL组比较，ox-LDL+ART组细胞活性、LC3-Ⅱ/LC3-Ⅰ比值、Bcl-2及TRPV4表达水平明显升高，而细胞凋亡率、Bax及p62表达水平明显降低，差异均有统计学意义(P<0.05)。与ox-LDL+ART组比较，ox-LDL+ART+3-MA组及ox-LDL+ART+RR组细胞活性、LC3-Ⅱ/LC3-Ⅰ比值、Bcl-2表达水平明显降低，细胞凋亡率、p62及Bax表达水平明显升高，差异均有统计学意义(P<0.05)。结论 ART可通过激活TRPV4促进细胞自噬，从而减轻ox-LDL诱导的血管内皮细胞损伤。

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袁向科，医学硕士，主治医师，主要从事中西医结合治疗周围血管疾病的基础及临床研究

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袁向科，医学硕士，主治医师，主要从事中西医结合治疗周围血管疾病的基础及临床研究

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J Cell Physiol, 2019, 234(5): 6831-6841., articleTitle=Knockdown of TRPV4 suppresses osteoclast differentiation and osteoporosis by inhibiting autophagy through Ca²⁺-calcineurin-NFATc1 pathway, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1211269164862411227, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, xref=1, ext=[AuthorCompanyExt(id=1211269164866605534, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, companyId=1211269164862411227, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹Department of Peripheral Vascular, Henan Province Hospital of TCM, Zhengzhou 450002, China), AuthorCompanyExt(id=1211269164874994141, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, companyId=1211269164862411227, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹河南省中医院周围血管科，郑州 450002)]), AuthorCompany(id=1211269164946297316, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, xref=2, ext=[AuthorCompanyExt(id=1211269164950491620, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, companyId=1211269164946297316, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²Department of Geriatrics, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450002, China), AuthorCompanyExt(id=1211269164958880230, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, companyId=1211269164946297316, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=²河南省中医药大学第三附属医院老年病科，郑州 450002)])], figs=[ArticleFig(id=1211269167798424136, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.1, caption=Effect of different concentrations of ox-LDL and ART on the viability of EA.hy926 cells (n=3), figureFileSmall=rEzOXRdXZPqsmVOzKo0iwg==, figureFileBig=h1ZQFH82rYpgsvrEhUTglQ==, tableContent=null), ArticleFig(id=1211269167882310221, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图1, caption=不同浓度ox-LDL、ART对EA.hy926细胞活性的影响(n=3)

与0 mg/ml ox-LDL组比较，(1)P<0.05；与50 mg/ml ox-LDL组比较，(2)P<0.05；与100 mg/ml ox-LDL组比较，(3)P<0.05；与150 mg/ml ox-LDL组比较，(4)P<0.05。

, figureFileSmall=rEzOXRdXZPqsmVOzKo0iwg==, figureFileBig=h1ZQFH82rYpgsvrEhUTglQ==, tableContent=null), ArticleFig(id=1211269168075248214, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.2, caption=Effect of ART on the viability of EA.hy926 cells induced by ox-LDL (n=3), figureFileSmall=MVpyNrV7SgeNUn10nCsFSQ==, figureFileBig=WX/LC9DAJy/U9LBdNO0hbw==, tableContent=null), ArticleFig(id=1211269168184300121, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图2, caption=ART对ox-LDL诱导的EA.hy926细胞活性的影响(n=3)

与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

, figureFileSmall=MVpyNrV7SgeNUn10nCsFSQ==, figureFileBig=WX/LC9DAJy/U9LBdNO0hbw==, tableContent=null), ArticleFig(id=1211269168280769117, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.3, caption=Effect of ART on the autophagy of EA.hy926 cells induced by ox-LDL (Western blotting, n=3), figureFileSmall=6deEJ3HTcdYvGREtoTDK2Q==, figureFileBig=n7b6hM6NZ7FsfRJJqaHz9Q==, tableContent=null), ArticleFig(id=1211269168360460896, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图3, caption=ART对ox-LDL诱导的EA.hy926细胞自噬的影响(Western blotting，n=3)

与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

, figureFileSmall=6deEJ3HTcdYvGREtoTDK2Q==, figureFileBig=n7b6hM6NZ7FsfRJJqaHz9Q==, tableContent=null), ArticleFig(id=1211269168469512805, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.4, caption=Effect of ART on the apoptosis of EA.hy926 cells induced by ox-LDL (n=3), figureFileSmall=oLQFpbMNvh0NJ6f7klrd7w==, figureFileBig=NuWQ75NRLY1wX93FJrOHhA==, tableContent=null), ArticleFig(id=1211269168565981800, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图4, caption=ART对ox-LDL诱导的EA.hy926细胞凋亡的影响(n=3)

A.流式细胞仪检测细胞凋亡；B.各组细胞凋亡率比较；C. Western blotting检测蛋白表达；D. 各组细胞蛋白表达水平比较；与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

, figureFileSmall=oLQFpbMNvh0NJ6f7klrd7w==, figureFileBig=NuWQ75NRLY1wX93FJrOHhA==, tableContent=null), ArticleFig(id=1211269168750531182, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.5, caption=Effect of ART on the protein expression of TRPV4 in EA.hy926 cells induced by ox-LDL (n=3), figureFileSmall=pN7OqFQjx/OSOuojb+4ZpQ==, figureFileBig=gO6WkNDznoYxxh6N/M3SuQ==, tableContent=null), ArticleFig(id=1211269169065103987, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图5, caption=ART对ox-LDL诱导的EA.hy926细胞TRPV4蛋白表达水平的影响(n=3)

与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

, figureFileSmall=pN7OqFQjx/OSOuojb+4ZpQ==, figureFileBig=gO6WkNDznoYxxh6N/M3SuQ==, tableContent=null), ArticleFig(id=1211269169165767284, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.6, caption=Effect of ART on the autophagy of EA.hy926 cells induced by ox-LDL (n=3), figureFileSmall=OVfam6j7oNNmTSZQ5aPk7Q==, figureFileBig=eRi0HUJjJ0Pivyc0o/uJiA==, tableContent=null), ArticleFig(id=1211269169308373624, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图6, caption=ART对ox-LDL诱导的EA.hy926细胞自噬的影响(n=3)

与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

, figureFileSmall=OVfam6j7oNNmTSZQ5aPk7Q==, figureFileBig=eRi0HUJjJ0Pivyc0o/uJiA==, tableContent=null), ArticleFig(id=1211269169442591360, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=EN, label=Fig.7, caption=Effect of suppressing TRPV4 on the viability and apoptosis of EA.hy926 cells induced by ox-LDL (n=3), figureFileSmall=Jx0VF09e0MtHnTGEYYisaw==, figureFileBig=bqZCBELQBwSlT6yBrwZJLg==, tableContent=null), ArticleFig(id=1211269169551643271, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269162010284312, language=CN, label=图7, caption=抑制TRPV4对ox-LDL诱导的EA.hy926细胞活性及细胞凋亡的影响(n=3)

A. 各组细胞活性比较；B. 各组细胞凋亡率比较；C. Western blotting检测各组细胞中Bcl-2及Bax蛋白的水平；D. 各组细胞Bcl-2及Bax蛋白表达水平比较；与对照组比较，(1)P<0.05；与ox-LDL组比较，(2)P<0.05；与ox-LDL+ART组比较，(3)P<0.05。

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