中药药理与临床2025，Vol.41Issue(10)：52-57,6.
丹参酮IIA介导CCND1/PLK1/CCNE2调节细胞周期促进H9C2心肌细胞再生
Tanshinone IIA-Mediated Regulation of Cell Cycle via CCND1/PLK1/CCNE2 to Promote H9C2 Cardiomyocyte Regeneration
摘要
Abstract
Objective:To observe the mechanism by which Tanshinone IIA(Tan IIA)promotes the regeneration of H9C2 cardiomyocytes after oxy-gen glucose deprivation/reoxygenation(OGD/R)injury.Methods:The experiment was divided into a normal control(NC)group,an OGD/R group,and Tan IIA groups at concentrations of 10,20,and 40 μmol/L.The CCK-8 assay was used to screen the protective concentrations of Tan IIA on OGD/R-injured H9C2 cardiomyocytes.Kits were used to detect the effects of Tan IIA on lactate dehydrogenase(LDH),creatine kinase MB(CK-MB),and creatine kinase(CK).Immunofluorescence was used to observe EdU proliferation in H9C2 cells.The wound-healing assay was used to assess the wound-healing ability of H9C2 cells.Transcriptome high-throughput sequencing was performed to explore the regenerative mechanisms of Tan IIA on H9C2 cardiomyocytes after OGD/R injury.Molecular docking was employed to analyze the binding between Tan IIA and differentially expressed proteins.Real-time polymerase chain reaction(real-time PCR)was used to validate the relative mRNA expression of differentially expressed genes Ccnd1/Plk1/Ccne2.Results:Compared with the OGD/R group,Tan IIA groups alleviated the damage caused by OGD/R to H9C2 cardiomyocytes,reduced LDH,CK,and CK-MB levels(P<0.01),and promoted cardiomyocyte regen-eration and wound healing(P<0.01,P<0.05).Transcriptome sequencing screened 623 differentially expressed genes.GO and KEGG en-richment analyses reveal that the regulation of differentially expressed genes by Tan IIA mainly affected biological processes such as protein folding,ribonucleoprotein complex,and unfolded protein binding,as well as pathways including protein processing in the endoplasmic reticu-lum,the FoxO signaling pathway,and the cell cycle.Molecular docking results show that the binding energies between Tan IIA and core dif-ferentially expressed proteins were all less than 6 kcal/mol.The relative mRNA expressions of Ccnd1/Plk1/Ccne2 were consistent with the transcriptome sequencing results.Conclusion:Tan IIA can mediate CCND1/PLK1/CCNE2 to regulate the cell cycle,thereby promoting the regeneration of H9C2 cardiomyocytes after OGD/R injury.关键词
丹参酮IIA/细胞周期/心肌细胞再生/OGD/R模型/周期蛋白/Polo样激酶Ⅰ/同期蛋白E1Key words
Tanshinone IIA/Cell cycle/Regeneration of H9C2 cardiomyocyte/OGD/R model/CCND1/PLK1/CCNE2引用本文复制引用
曹策,刘建勋,辛高杰,刘子馨,张会雨,陈原原,郭帆,彭涵,李磊,付建华..丹参酮IIA介导CCND1/PLK1/CCNE2调节细胞周期促进H9C2心肌细胞再生[J].中药药理与临床,2025,41(10):52-57,6.基金项目
国家自然基金重点资助项目(编号:82030124、82174015) （编号:82030124、82174015）
中国中医科学院西苑医院能力提升项目(编号:XYZX0303-03) （编号:XYZX0303-03）
中国中医科学院科技创新工程(编号:CI2021A04609). （编号:CI2021A04609）
