目的 探讨三七皂苷R₁（notoginsenoside R₁，NGR1）对小鼠心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury，MIRI）后心脏重塑的影响及其机制。方法 通过结扎小鼠冠状动脉前降支并再灌注构建MIRI后心脏重塑模型，给予NGR1干预3周。测定小鼠心脏指数、心胫比；采用小动物超声仪检测左室舒张末期容积（left ventricular end-diastolic volume，LVEDV）、左室收缩末期容积（left ventricular end-systolic volume，LVESV）、左室射血分数（left ventricular ejection fraction，LVEF）、左室短轴缩短率（left ventricular fractional shortening，LVFS）；通过小麦胚芽凝集素（wheat germ agglutinin，WGA）荧光染色检测心肌细胞横截面积；Masson染色计算心脏胶原体积分数（collagen volume fraction，CVF）；Western blotting检测心肌组织collagen I、collagen III、心房利钠肽（atrial natriuretic peptide，ANP）、脑钠肽（brain natriuretic peptide，BNP）、转铁蛋白受体1（transferrin receptor 1，TFR1）、酰基辅酶A合成酶长链家族成员4（acyl-CoA synthetase long-chain family member 4，ACSL4）、溶质载体家族7成员11（solute carrier family 7 member 11，SLC7A11）、谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）的蛋白表达；通过网络药理学初步探讨NGR1抑制MIRI后心脏重塑的可能机制；采用试剂盒检测心肌组织亚铁离子（Fe²⁺）、脂质过氧化物（lipid peroxide，LPO）含量；通过透射电镜观察心肌线粒体损伤情况。结果 与假手术组比较，模型组小鼠心脏指数、心胫比、LVEDV、LVESV、CVF显著升高（P＜0.05、0.01），心肌组织collagen Ⅰ、collagen Ⅲ、ANP、BNP、TFR1和ACSL4蛋白表达水平显著升高（P＜0.01），Fe²⁺、LPO含量显著升高（P＜0.05、0.01），线粒体膜密度增加及嵴减少，SLC7A11、GPX4蛋白表达水平显著降低（P＜0.01）。与模型组比较，NGR1给药组小鼠心脏指数、心胫比、LVEDV、LVESV、CVF显著降低（P＜0.05、0.01），心肌组织collagen Ⅰ、collagen Ⅲ、ANP、BNP、TFR1和ACSL4蛋白表达水平显著降低（P＜0.05、0.01），Fe²⁺、LPO含量显著降低（P＜0.05、0.01），线粒体损伤改善，SLC7A11、GPX4蛋白表达水平显著升高（P＜0.05、0.01）。结论 NGR1可显著改善小鼠MIRI后心脏重塑，其机制可能与激活SLC7A11/GPX4通路以抑制心肌细胞铁死亡有关。

Objective To investigate the effect and mechanism of notoginsenoside R₁ (NGR1) on cardiac remodeling after myocardial ischemia-reperfusion injury (MIRI) in mice. Methods A model of cardiac remodeling after myocardial ischemia-reperfusion injury (MIRI) was established by ligating the anterior descending branch of the coronary artery in mice. After three weeks of intervention with NGR1, the cardiac index and heart weight/tibia length of mice were measured. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured using a small animal ultrasound instrument. The cross-sectional area of myocardial cells was calculated by wheat germ agglutinin (WGA) fluorescence staining. The collagen volume fraction (CVF) of heart was calculated by Masson staining. The protein expressions of collagen I, collagen III, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transferrin receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in myocardial tissue were detected by Western blotting. The possible mechanism of NGR1 inhibiting cardiac remodeling after MIRI was preliminarily explored through network pharmacology. The contents of iron ions (Fe²⁺) and lipid peroxide (LPO) in myocardial tissue were detected using kits. The damage of myocardial mitochondria was observed by transmission electron microscopy. Results Compared with sham group, cardiac index, heart weight/tibia length, LVEDV, LVESV and CVF of mice in model group were significantly increased (P < 0.05, 0.01), protein expressions of collagen I, collagen III, ANP, BNP, TFR1 and ACSL4 in myocardial tissue were significantly increased (P < 0.01), contents of Fe²⁺ and LPO were significantly increased (P < 0.05, 0.01), mitochondrial membrane density was increased and cristae was decreased, SLC7A11 and GPX4 protein expressions were significantly decreased (P < 0.01). Compared with model group, cardiac index, heart weight/tibia length, LVEDV, LVESV and CVF of mice in NGR1 administration groups were significantly decreased (P < 0.05, 0.01), protein expressions of collagen I, collagen III, ANP, BNP, TFR1 and ACSL4 were significantly decreased (P < 0.05, 0.01), contents of Fe²⁺ and LPO were significantly decreased (P < 0.05, 0.01), mitochondrial damage was improved, SLC7A11 and GPX4 protein expressions were significantly increased (P < 0.05, 0.01). Conclusion NGR1 could significantly improve cardiac remodeling in mice after MIRI, and its mechanism may be related to the activation of SLC7A11/GPX4 pathway to inhibit ferroptosis of cardiomyocytes.

R285.5

国家自然科学基金资助项目(82574623);国家自然科学基金资助项目(82260987);贵州省高层次创新型人才项目(黔科合平台人才-GCC[2023]048);贵州省教育厅“百校千企科技攻关揭榜挂帅”项目(黔教技[2025]017号);贵州省研究生科研基金资助项目(2024YJSKYJJ355);贵州中医药大学研究生创新计划项目(YCXKYB2025018)