Article(id=1195816326469043119, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, articleNumber=1001-2494(2024)24-2337-06, orderNo=null, doi=10.11669/cpj.2024.24.006, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1718640000000, receivedDateStr=2024-06-18, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1763034429423, onlineDateStr=2025-11-13, pubDate=1734796800000, pubDateStr=2024-12-22, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763034429423, onlineIssueDateStr=2025-11-13, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763034429423, creator=13701087609, updateTime=1763034429423, updator=13701087609, issue=Issue{id=1195816324862624679, tenantId=1146029695717560320, journalId=1190317699101192196, year='2024', volume='59', issue='24', pageStart='2299', pageEnd='2406', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763034429040, creator=13701087609, updateTime=1763034724390, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1195817563738390939, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1195817563738390940, tenantId=1146029695717560320, journalId=1190317699101192196, issueId=1195816324862624679, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2337, endPage=2342, ext={EN=ArticleExt(id=1195816326670369712, articleId=1195816326469043119, tenantId=1146029695717560320, journalId=1190317699101192196, language=EN, title=Effect of Stachydrine on Hypoxia/Reoxygenation Induced Cardiomyocyte Pyroptosis by Regulating the HIF-1α/NLRP3 Signaling Pathway, columnId=null, journalTitle=Chinese Pharmaceutical Journal, columnName=null, runingTitle=null, highlight=null, articleAbstract=

OBJECTIVE To investigate the effect of stachydrine (STA) on hypoxia inducible factor-1α (HIF-1α)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in hypoxia/reoxygenation (H/R) induced cardiomyocyte pyroptosis model. METHODS H9C2 cardiomyocytes were separated into control group (Control group), model group (H/R group), H/R+low concentration STA group (H/R+STA-L group, 5 μmol·L^-1), H/R+medium concentration STA group (H/R+STA-M group, 10 μmol·L^-1), H/R+high concentration STA group (H/R+STA-H group, 20 μmol·L^-1), H/R+high concentration STA (20 μmol·L^-1)+HIF-1α activator group [H/R+STA-H+dimethyloxaloglycine(DMOG) group, 20 μmol·L^-1 STA+10 μmol·L^-1 DMOG]. H9C2 cell viability was tested by cell counting kit-8(CCK-8) assay. H9C2 cell apoptosis was measured by flow cytometry. The levels of IL-1β, IL-18, and LDH in cells were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of IL-1β, IL-18, Caspase-1, HIF-1α, and NLRP3 were quantified using Western blot. RESULTS Compared with the control group, the cell survival rate of the H/R group decreased (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 increased (P<0.05). Compared with the H/R group, the cell survival rates of the H/R+STA-L group, H/R+STA-M group and H/R+STA-H group increased, the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 reduced (P<0.05). Compared with the H/R+STA-H group, the cell survival rate of the H/R+STA-H+DMOG group obviously reduced (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 obviously increased (P<0.05). CONCLUSION STA can inhibit H/R induced cardiomyocyte pyroptosis, and its mechanism may be related to the HIF-1α/NLRP3 signaling pathway.

, correspAuthors=Xiaoping ZHANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Xiaoli LI, Tao WANG, Chuanfang DONG, Yanan XU, Xiaoping ZHANG), CN=ArticleExt(id=1195816476574793945, articleId=1195816326469043119, tenantId=1146029695717560320, journalId=1190317699101192196, language=CN, title=水苏碱调节HIF-1α/NLRP3信号通路对缺氧/复氧诱导的心肌细胞焦亡的影响, columnId=1190352405612040510, journalTitle=中国药学杂志, columnName=论著, runingTitle=null, highlight=null, articleAbstract=

目的 研究水苏碱(stachydrine,STA)对缺氧/复氧(hypoxia/reoxygenation,H/R)诱导的心肌细胞焦亡模型缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)/NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)信号通路的影响。方法 将心肌细胞H9C2细胞分为对照组(Control组)、模型组(H/R组)、H/R+低浓度STA组(H/R+STA-L组,5 μmol·L^-1)、H/R+中浓度STA组(H/R+STA-M组,10 μmol·L^-1)、H/R+高浓度STA组(H/R+STA-H组,20 μmol·L^-1)、H/R+高浓度STA(20 μmol·L^-1)+HIF-1α激活剂组[H/R+STA-H+二甲基草酰甘氨酸(DMOG)组,20 μmol·L^-1的STA+10 μmol·L^-1 DMOG]。细胞计数试剂盒8(CCK-8)检测H9C2细胞活性;流式细胞仪检测H9C2细胞焦亡;酶联免疫吸附法(ELISA)检测细胞白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、乳酸脱氢酶(LDH)水平。蛋白质印迹(Western blot)检测IL-1β、IL-18、半胱天冬酶-1(Caspase-1)、HIF-1α、NLRP3表达。结果 与Control组比较,H/R组细胞存活率降低(P<0.05),Caspase-1阳性表达率、IL-1β、IL-18、LDH水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3蛋白表达升高(P<0.05);与H/R组比较,H/R+STA-L组、H/R+STA-M组、H/R+STA-H组细胞存活率增加,Caspase-1阳性表达率、IL-1β、IL-18、LDH水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3蛋白表达降低(P<0.05);与H/R+STA-H组比较,H/R+STA-H+DMOG组的细胞存活率显著降低(P<0.05),Caspase-1阳性表达率、IL-1β、IL-18、LDH水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3蛋白表达显著升高(P<0.05)。结论 STA能够抑制H/R诱导的心肌细胞焦亡,其机制可能与HIF-1α/NLRP3信号通路相关。

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李效丽,女,硕士,主治医师 研究方向:老年心脑血管病

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李效丽,女,硕士,主治医师 研究方向:老年心脑血管病

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Chin Med, 2022, 17(1): 73., articleTitle=Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury, refAbstract=null)], funds=[Fund(id=1196081680059511177, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, awardId=2023BJ000005, language=CN, fundingSource=山东省医药卫生科研项目(2023BJ000005), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1196081675458359628, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, xref=1, ext=[AuthorCompanyExt(id=1196081675462553933, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, companyId=1196081675458359628, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹ Department of Special Health Care, 1b.Department of geriatrics, The Third Hospital of Shandong Province, Jinan 250031, China), AuthorCompanyExt(id=1196081675470942542, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, companyId=1196081675458359628, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=¹ 山东省立第三医院, a.特需保健科, b.老年病科, 济南 250031)]), AuthorCompany(id=1196081675563217232, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, xref=2, ext=[AuthorCompanyExt(id=1196081675571605841, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, companyId=1196081675563217232, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=² Department of General Medicine, 960 Hospital of PLA, Jinan 250031, China), AuthorCompanyExt(id=1196081675579994450, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, companyId=1196081675563217232, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=² 解放军第九六零医院全科医学科, 济南 250031)])], figs=[ArticleFig(id=1196081678088188287, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=EN, label=Fig.1, caption=The effect of STA on the activity of H9C2 cells. n=6,$\bar{x}±s$

¹⁾P<0.05, vs Control group; ²⁾P<0.05, vs H/R group; ³⁾P<0.05, vs H/R+STA-L group; ⁴⁾P<0.05, vs H/R+STA-M group; ⁵⁾P<0.05, vs H/R+STA-H group.

, figureFileSmall=Rn4lOWpp/QEY1SXUHU15qw==, figureFileBig=XXG/pgaFpPlxCxkojV3XTA==, tableContent=null), ArticleFig(id=1196081678146908544, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=CN, label=图1, caption=水苏碱(STA)对H9C2细胞活性的影响。n=6,$\bar{x}±s$

与Control组相比,¹⁾P<0.05;与H/R组相比,²⁾P<0.05;与H/R+STA-L组相比,³⁾P<0.05;与H/R+STA-M组相比,⁴⁾P<0.05;与H/R+STA-H组相比,⁵⁾P<0.05。

, figureFileSmall=Rn4lOWpp/QEY1SXUHU15qw==, figureFileBig=XXG/pgaFpPlxCxkojV3XTA==, tableContent=null), ArticleFig(id=1196081678243377537, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=EN, label=Fig.2, caption=The effect of STA on pyroptosis in H9C2 cells. n=6,$\bar{x}±s$

A-flow cytometry was used to detect cell pyroptosis (Caspase-1+PI); B-comparison of Caspase-1 positive expression rates. ¹⁾P<0.05, vs control group; ²⁾P<0.05, vs H/R group; ³⁾P<0.05, vs H/R+STA-L group; ⁴⁾P<0.05, vs H/R+STA-M group; ⁵⁾P<0.05, vs H/R+STA-H group.

, figureFileSmall=Qco1Bjrmf+ffrEeyAgHt5w==, figureFileBig=ExOpioHj1mFMYmEGcHU+JA==, tableContent=null), ArticleFig(id=1196081679321313666, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=CN, label=图2, caption=STA对H9C2细胞焦亡的影响。n=6,$\bar{x}±s$

A-流式细胞术检测细胞焦亡[半胱天冬酶-1(Caspase-1)+PI];B-Caspase-1阳性表达率比较。与Control组相比,¹⁾P<0.05;与H/R组相比,²⁾P<0.05;与H/R+STA-L组相比,³⁾P<0.05;与H/R+STA-M组相比,⁴⁾P<0.05;与H/R+STA-H组相比,⁵⁾P<0.05。

, figureFileSmall=Qco1Bjrmf+ffrEeyAgHt5w==, figureFileBig=ExOpioHj1mFMYmEGcHU+JA==, tableContent=null), ArticleFig(id=1196081679396811139, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=EN, label=Fig.3, caption=Protein levels of Caspase-1, IL-1 β and IL-18 in H9C2 cells of each group.n=6,$\bar{x}±s$

A-Western blot was used to detect the protein expression of Caspase-1, IL-1β, and IL-18 in H9C2 cells; B-comparison of Caspase-1, IL-1β, and IL-18 protein levels. ¹⁾P<0.05, vs Control group; ²⁾P<0.05, vs H/R group; ³⁾P<0.05, vs H/R+STA-L group; ⁴⁾P<0.05, vs H/R+STA-M group; ⁵⁾P<0.05, vs H/R+STA-H group.

, figureFileSmall=jtk/+0f7g4GD52YavoH33g==, figureFileBig=3C+3R6WWR1t/POOuLSV0sw==, tableContent=null), ArticleFig(id=1196081679472308612, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=CN, label=图3, caption=各组H9C2细胞中Caspase-1、IL-1β、IL-18蛋白水平。n=6,$\bar{x}±s$

A-Western blot检测H9C2细胞中Caspase-1、IL-1β、IL-18蛋白表达;B-Caspase-1、IL-1β、IL-18蛋白水平比较。与Control组相比,¹⁾P<0.05;与H/R组相比,²⁾P<0.05;与H/R+STA-L组相比,³⁾P<0.05;与H/R+STA-M组相比,⁴⁾P<0.05;与H/R+STA-H组相比,⁵⁾P<0.05。

, figureFileSmall=jtk/+0f7g4GD52YavoH33g==, figureFileBig=3C+3R6WWR1t/POOuLSV0sw==, tableContent=null), ArticleFig(id=1196081679581360517, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=EN, label=Fig.4, caption=Levels of HIF-1α/NLRP3 signaling pathway related proteins in H9C2 cells of each group.n=6,$\bar{x}±s$

A-Western blot was used to detect the expression of HIF-1α and NLRP3 proteins in H9C2 cells; B-comparison of HIF-1α and NLRP3 protein levels; ¹⁾P<0.05, vs control group; ²⁾P<0.05, vs H/R group; ³⁾P<0.05, vs H/R+STA-L group; ⁴⁾P<0.05, vs H/R+STA-M group; ⁵⁾P<0.05, vs H/R+STA-H group.

, figureFileSmall=b8hfOIcfPsl5SuHkMEmIVw==, figureFileBig=0BtYJhS7P5BDVfsDZ0AriQ==, tableContent=null), ArticleFig(id=1196081679665246598, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=CN, label=图4, caption=各组H9C2细胞中缺氧诱导因子-1α(HIF-1α)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路相关蛋白水平。n=6,$\bar{x}±s$

A-Western blot检测H9C2细胞中HIF-1α、NLRP3蛋白表达;B-HIF-1α、NLRP3蛋白水平比较。与Control组相比,¹⁾P<0.05;与H/R组相比,²⁾P<0.05;与H/R+STA-L组相比,³⁾P<0.05;与H/R+STA-M组相比,⁴⁾P<0.05;与H/R+STA-H组相比,⁵⁾P<0.05。

, figureFileSmall=b8hfOIcfPsl5SuHkMEmIVw==, figureFileBig=0BtYJhS7P5BDVfsDZ0AriQ==, tableContent=null), ArticleFig(id=1196081679736549767, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=EN, label=Tab.1, caption=

Effects of STA on IL-1β, IL-18, and LDH levels in H9C2 cells.n=6,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=

Group	ρ(IL-1β)/pg·mL-1	ρ(IL-18)/pg·mL-1	LDH/U·L-1
Control	9.29±0.11	13.56±1.41	122.18±13.25
H/R	41.57±4.231)	42.39±4.361)	226.49±23.611)
H/R+STA-L	32.59±3.512)	35.39±3.652)	165.24±17.242)
H/R+STA-M	23.16±2.452)3)	26.37±2.712)3)	152.36±16.362)3)
H/R+STA-H	12.56±1.372)3)4)	17.28±2.322)3)4)	131.25±13.512)3)4)
H/R+STA-H+DMOG	38.75±0.415)	38.51±3.975)	206.31±13.225)

), ArticleFig(id=1196081679866573192, tenantId=1146029695717560320, journalId=1190317699101192196, articleId=1195816326469043119, language=CN, label=表1, caption=

STA对H9C2细胞中白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、乳酸脱氢酶(LDH)水平的影响。n=6,$\bar{x}±s$

, figureFileSmall=null, figureFileBig=null, tableContent=

Group	ρ(IL-1β)/pg·mL-1	ρ(IL-18)/pg·mL-1	LDH/U·L-1
Control	9.29±0.11	13.56±1.41	122.18±13.25
H/R	41.57±4.231)	42.39±4.361)	226.49±23.611)
H/R+STA-L	32.59±3.512)	35.39±3.652)	165.24±17.242)
H/R+STA-M	23.16±2.452)3)	26.37±2.712)3)	152.36±16.362)3)
H/R+STA-H	12.56±1.372)3)4)	17.28±2.322)3)4)	131.25±13.512)3)4)
H/R+STA-H+DMOG	38.75±0.415)	38.51±3.975)	206.31±13.225)

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