中国药物警戒 ›› 2025, Vol. 22 ›› Issue (12): 1334-1339.
DOI: 10.19803/j.1672-8629.20250753

• 心脑血管中药作用机制与安全性评价专栏 • 上一篇    下一篇

基于转录组学研究双参宁心胶囊抗小鼠心肌梗死的作用机制

白雪1, 刘建勋2#, 李雪丽1*   

  1. 1中国中医科学院医学实验中心,北京市中医药防治重大疾病基础研究重点实验室,北京 100700;
    2中国中医科学院西苑医院基础医学研究所,北京 100091
  • 收稿日期:2025-10-31 发布日期:2025-12-19
  • 通讯作者: *李雪丽,女,博士,副研究员,中药防治心脑血管疾病。E-mail: emilia1801@qq.com;#为共同通信作者。
  • 作者简介:白雪,女,博士,助理研究员,中药防治心脑血管疾病。
  • 基金资助:
    国家自然科学基金资助项目（82204670、82304767）; 中央级公益性科研院所基本科研业务费专项基金（ZZ13-YQ-081、ZZ15-YQ-055、XTCX2023002）; 中国中医科学院科技创新工程项目（CI2021B017）

Mechanisms of Shuangshen Ningxin Capsule against Myocardial Infarction in Mice Based on Transcriptomics

BAI Xue1, LIU Jianxun2#, LI Xueli1*   

  1. 1Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease, Beijing 100700, China;
    2Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
  • Received:2025-10-31 Published:2025-12-19

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摘要： 目的 结合转录组学研究双参宁心胶囊（SSNXAIG）抗小鼠心肌梗死（MI）作用及机制。方法 挤心脏法结合结扎冠状动脉左前降支（LAD）建立小鼠MI模型。雄性C57BL/6J小鼠随机分为假手术组（Sham组）,模型组（MI组）, SSNXAIG低（SSNXAIG-L）和高（SSNXAIG-H）剂量组,每组9只。SSNXAIG-L组和SSNXAIG-H组分别灌胃0.125和0.250 g·kg-1·d-1的SSNXAIG混悬液,Sham组和MI组灌胃等体积蒸馏水,连续给药14 d;采用超声多普勒检测小鼠的心脏功能,并计算小鼠心脏指数,苏木精-伊红染色（HE）观察心肌组织病理形态特征,Masson染色观察心肌组织纤维化程度,通过转录组测序筛选差异表达基因（DEGs）并进行GO功能注释和KEGG富集分析。结果 与MI组比较,SSNXAIG-H组心脏指数明显降低（P<0.01）,SSNXAIG-L组和SSNXAIG-H组左心室射血分数（LVEF）和左室短轴缩短率（LVFS）均显著升高（P<0.01）,SSNXAIG-L组和SSNXAIG-H组小鼠心肌损伤减轻,炎性细胞浸润减少,心肌纤维化程度降低。转录组测序结果显示,Sham组与MI组筛选出2 243个DEGs,1 815个上调基因、428个下调基因。MI组与SSNXAIG组筛选出94个DEGs,13个上调基因、81个下调基因,且其中87个DEGs呈现逆转趋势。KEGG信号通路分析显示,DEGs主要富集在细胞周期、细胞衰老和p53信号通路。结论 SSNXAIG明显减小MI小鼠心肌损伤、改善心功能和减轻心肌纤维化,其作用机制可能与调节细胞周期、细胞衰老和p53信号通路相关。

关键词: 心肌梗死, 双参宁心胶囊, 转录组学, 差异基因, 小鼠

Abstract: Objective To investigate the role and mechanism of Shuangshen Ningxin capsules (SSNXAIG) against myocardial infarction (MI) in mice via transcriptomics. Methods MI models were established in male C57BL/6J mice via cardiac compression combined with ligation of the left anterior descending artery (LAD). Mice were randomly divided into the sham group, MI model group, low dose of SSNXAIG (SSNXAIG-L) group, and high dose of SSNXAIG (SSNXAIG-H) group, with 9 in each group. The SSNXAIG-L group was given SSNXAIG suspension (0.125 g·kg-1·d-1), the SSNXAIG-H group received SSNXAIG suspension (0.250 g·kg-1·d-1), and the sham group and MI group were given double distilled water. Intragastric treatment lasted for 14 days. Cardiac indexes were measured. Cardiac function was assessed with Doppler ultrasound. Myocardial pathology was observed via HE staining while fibrosis was evaluated by Masson's trichrome staining. Differentially expressed genes (DEGs) were screened via RNA-seq, followed by GO annotation and KEGG enrichment analysis. Results Compared with the MI group, cardiac indexes were significantly reduced in the SSNXAIG-H group (P<0.01) while LVEF and LVFS were increased in SSNXAIG-L and SSNXAIG-H groups (P<0.01), and both doses mitigated myocardial injury, inflammatory infiltration and fibrosis. The transcriptome sequencing results showed that there were 2 243 DEGs (1 815 upregulated and 428 downregulated) in Sham and MI groups, 94 DEGs (13 upregulated and 81 downregulated) in MI and SSNXAIG groups, with 87 DEGs tending to be reversed. KEGG pathway analysis revealed that DEGs were primarily enriched in cell cycle, cellular senescence, and the p53 signaling pathway. Conclusion SSNXAIG can significantly reduce myocardial injury, improve cardiac function, and attenuate myocardial fibrosis in MI mice. The underlying mechanism may be associated with the modulation of cell cycle, cellular senescence, and the p53 signaling pathway.

Key words: Myocardial Infarction, Shuangshen Ningxin Capsule, Transcriptomics, Differentially Expressed Genes, Mice

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