天津医药

天津医药 ›› 2026, Vol. 54 ›› Issue (1): 23-29.doi: 10.11958/20252283

• 实验研究 • 上一篇    下一篇

基于miR-144-3p/MAPK1通路探讨红参总皂苷对扩张型心肌病小鼠心肌细胞凋亡的影响

李志伟1(), 张会超2, 杨凤鸣2, 曾垂义2,△()   

  1. 1 河南省中医院（河南中医药大学第二附属医院）心血管科（邮编450045）
    2 河南省中医院（河南中医药大学第二附属医院）心病科
  • 收稿日期:2025-06-19 修回日期:2025-08-29 出版日期:2026-01-15 发布日期:2026-01-19
  • 通讯作者: △ E-mail：13939018435@163.com
  • 作者简介:李志伟（1987），女，主治医师，主要从事中医治疗心血管疾病方面研究。E-mail：Friday001407@163.com
  • 基金资助:
    河南省科技攻关项目(222102310482);河南省中医药拔尖人才培养项目(豫卫中医函[2021]15号);河南省特色骨干学科中医学学科建设项目(STG-ZYXKY-2020013)

Exploring the effect of red ginseng total saponins on cardiomyocyte apoptosis in dilated cardiomyopathy mice based on miR-144-3p/MAPK1 pathway

LI Zhiwei1(), ZHANG Huichao2, YANG Fengming2, ZENG Chuiyi2,△()   

  1. 1 Department of Cardiovascular Medicine, Henan Province Hospital of TCM (the Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou 450045, China
    2 Department of Cardiology, Henan Province Hospital of TCM (the Second Affiliated Hospital of Henan University of Chinese Medicine)
  • Received:2025-06-19 Revised:2025-08-29 Published:2026-01-15 Online:2026-01-19
  • Contact: △ E-mail：13939018435@163.com

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摘要：

目的 探讨红参总皂苷（RGTS）调节微小RNA-144-3p（miR-144-3p）/丝裂原活化蛋白激酶1（MAPK1）通路对扩张型心肌病（DCM）小鼠心肌细胞凋亡的影响。方法 采用双萤光素酶报告基因实验分析miR-144-3p与MAPK1之间的靶向关系。选取10只C57BL/6J小鼠为对照（Control）组，另将转基因DCM小鼠随机分为DCM组、卡托普利（CAP，10.1 mg/kg）组、低剂量RGTS（L-RGTS）组（6 g/kg）、高剂量RGTS（H-RGTS）组（12 g/kg）、阴性对照（NC antagomir）组（灌胃12 g/kg RGTS+尾静脉注射NC antagomir）、miR-144-3p抑制剂（miR-144-3p antagomir）组（灌胃12 g/kg RGTS+尾静脉注射miR-144-3p antagomir），每组10只。采用超声心动仪评估小鼠心功能；实时荧光定量PCR（qRT-PCR）检测心肌组织中miR-144-3p和MAPK1 mRNA的表达；HE染色观察心肌组织病理变化；TUNEL染色检测心肌细胞凋亡；Western blot法检测Bax、MAPK1蛋白表达。结果 Control组心肌细胞排列整齐；DCM组心肌细胞排列紊乱，可见细胞肿胀、坏死和核固缩；CAP组、L-RGTS组、H-RGTS组及NC antagomir组心肌细胞排列较为整齐，肿胀不明显；miR-144-3p antagomir组心肌细胞排列紊乱。双萤光素酶报告基因实验证实miR-144-3p可靶向负调控MAPK1。与Control组相比，DCM组左室收缩期内径（LVESD）、左室舒张末内径（LVEDD）、MAPK1 mRNA和蛋白、Bax蛋白表达水平及细胞凋亡率均升高，左室射血分数（LVEF）、左室短轴缩短率（LVFS）和miR-144-3p表达水平降低（P<0.05）。与DCM组相比，CAP组、L-RGTS组和H-RGTS组LVESD、LVEDD、MAPK1 mRNA和蛋白、Bax蛋白表达水平及细胞凋亡率均降低，LVEF、LVFS和miR-144-3p表达水平升高（P<0.05）；且H-RGTS组上述指标变化较L-RGTS组显著（P<0.05）。与H-RGTS组和NC antagomir组相比，miR-144-3p antagomir组上述指标变化被逆转（P<0.05）。结论 RGTS可能通过调控miR-144-3p/MAPK1通路抑制DCM小鼠心肌细胞凋亡。

关键词: 心肌病, 扩张型, 丝裂原活化蛋白激酶1, 细胞凋亡, 红参总皂苷, 微小RNA-144-3p

Abstract:

Objective To investigate the effect of red ginseng total saponins (RGTS) on cardiomyocyte apoptosis in dilated cardiomyopathy (DCM) mice by regulating microRNA-144-3p (miR-144-3p)/mitogen activated protein kinase 1 (MAPK1) pathway. Methods The targeting relationship between miR-144-3p and MAPK1 was analyzed via dual luciferase reporter gene assay. Ten C57BL/6J mice were included as the control group, and the transgenic DCM mice were randomly assigned into the DCM group, the captopril group (CAP, 10.1 mg/kg), the low-dose RGTS (L-RGTS) group, the high-dose RGTS (H-RGTS) group (gavage of 6 and 12 g/kg RGTS), the negative control (NC antagomir) group (gavage of 12 g/kg RGTS+tail vein injection of NC antagomir) and the miR-144-3p antagomir group (gavage of 12 g/kg RGTS+tail vein injection of miR-144-3p antagomir), each had 10 mice. The DCM group and the control group were given equal amount of physiological saline by gavage and tail vein injection, once a day for 8 weeks. Echocardiography was used to detect cardiac function in DCM mice. Quantitative real-time fluorescence PCR (qRT-PCR) was used to detect miR-144-3p and MAPK1 mRNA in myocardial tissue. HE staining was used to detect pathological changes in myocardial tissue. TUNEL staining was used to detect cardiomyocyte apoptosis. Western blot assay was used to measure Bax and MAPK1 protein expression in myocardial tissue. Results The control group had a regular arrangement of cardiomyocytes. The arrangement of cardiomyocytes in the DCM group was irregular, with visible cell swelling, necrosis and nuclear condensation. The cardiomyocyte arrangement was relatively regular, and cell swelling was not prominent in the CAP group, the L-RGTS group, the H-RGTS group and the NC antagomir group. The miR-144-3p antagomir group had irregular arrangement of cardiomyocytes. The dual-luciferase reporter gene assay confirmed that miR-144-3p can specifically and negatively regulate MAPK1. Compared with the control group, the left ventricular systolic inner diameter (LVESD), left ventricular diastolic end diameter (LVEDD), expression levels of MAPK1 mRNA and protein, Bax protein and cell apoptosis rate were all increased in the DCM group, while the left ventricular ejection fraction (LVEF), left ventricular short-axis shortening rate (LVFS), and expression level of miR-144-3p were decreased (P<0.05). Compared with the DCM group, the expression levels of LVESD, LVEDD, MAPK1 mRNA and protein, Bax protein, as well as the apoptosis rate were all decreased in the CAP group, the L-RGTS group and the H-RGTS group, while the expression levels of LVEF, LVFS and miR-144-3p were increased (P<0.05). Changes of the above indicators were more significant in the H-RGTS group than those in the L-RGTS group (P<0.05). Compared with the H-RGTS group and the NC antagomir group, the changes of the above indicators were reversed in the miR-144-3p antagomir group (P<0.05). Conclusion RGTS may regulate the miR-144-3p/MAPK1 pathway to inhibit cardiomyocyte apoptosis in DCM mice.

Key words: cardiomyopathy, dilated, mitogen-activated protein kinase 1, apoptosis, red ginseng total saponins, microRNA-144-3p

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