2025 年第 3 期 第 20 卷

芹菜素对心肌梗死模型大鼠心功能的保护作用及其可能机制研究

Protective effect of apigenin on cardiac function in rats with myocardial infarction and its possible mechanism

作者：苗艳霞1李艳2时宝林3张跃其3吴春丽4

英文作者：Miao Yanxia1 Li Yan2 Shi Baolin3 Zhang Yueqi3 Wu Chunli4

单位：1山东省潍坊市人民医院健康管理中心，潍坊261000；2山东省潍坊市人民医院神经外科，潍坊261000；3山东省潍坊市人民医院神经内科，潍坊261000；4山东省潍坊市人民医院产科医学中心，潍坊261000

英文单位：1Health Management Center Weifang People′s Hospital Shandong Province Weifang 261000 China; 2Department of Neurosurgery Weifang People′s Hospital Shandong Province Weifang 261000 China; 3Department of Neurology Weifang People′s Hospital Shandong Province Weifang 261000 China; 4Department of Obstetrics Medical Center Weifang People′s Hospital Shandong Province Weifang 261000 China

关键词：心肌梗死；芹菜素；过氧化物酶体增殖物激活受体γ；信号通路

英文关键词：Myocardialinfarction;Apigenin;Peroxisomeproliferation-activatedreceptorsγ;Signalingpathway

• 摘要：

• 目的 探讨芹菜素对心肌梗死模型大鼠心功能的保护作用及其通过去乙酰化酶3/β-连环蛋白/过氧化物酶体增殖物激活受体γ（PPARγ）信号通路的潜在作用机制。方法 选取40只健康成年雄性无特定病原体级SD大鼠完全随机分为假手术组、心肌梗死组、芹菜素组以及芹菜素+GW9662（一种PPARγ拮抗剂）组，每组10只。除假手术组外，其余各组均建立大鼠心肌梗死模型，而后心肌梗死组不给予其他干预，芹菜素组每日腹腔注射芹菜素5 mg/kg连续7 d，芹菜素+GW9662组在芹菜素组基础上每日腹腔注射GW9662 2 mg/kg连续7 d。比较各组心肌酶水平、心肌形态、炎症因子水平、心肌细胞凋亡率以及心肌组织中的去乙酰化酶3、β-连环蛋白和PPARγ的表达水平。结果 去除死亡大鼠后，每组随机选出6只进行各项检测。心肌梗死组肌酸激酶同工酶及心肌肌钙蛋白I水平均明显高于假手术组（均P<0.001），而芹菜素组二者水平均明显低于心肌梗死组［（41±6）U/L比（118±14）U/L、（4.6±1.8）ng/L比（14.2±2.2）ng/L］（均P<0.001），芹菜素+GW9662组二者水平均显著高于芹菜素组(均P<0.01)。芹菜素组细胞形态和排列较心肌梗死组恢复，横纹较清晰，细胞坏死减少。芹菜素组白细胞介素1β、白细胞介素6水平均明显低于心肌梗死组（均P<0.01），而芹菜素+GW9662组二者水平均显著高于芹菜素组（均P<0.05）。假手术组、心肌梗死组、芹菜素组、芹菜素+GW9662组心肌细胞凋亡率分别为2.95%、38.78%、12.56%、22.33%。芹菜素组心肌组织中去乙酰化酶3及PPARγ蛋白水平均显著高于心肌梗死组，β-连环蛋白水平低于心肌梗死组（均P<0.001）；芹菜素+GW9662组中去乙酰化酶3及PPARγ蛋白水平均显著低于芹菜素组（P<0.05或P<0.01），β-连环蛋白水平高于芹菜素组（P<0.05）。结论 芹菜素通过激活去乙酰化酶3/β-连环蛋白/PPARγ信号通路，显著改善心肌梗死后的心功能，并减少心肌细胞凋亡，其保护心脏的机制可能涉及调节这一信号通路。PPARγ的激活对芹菜素的心脏保护效果至关重要。

• Objective  To investigate the protective effect of apigenin on cardiac function in rats with myocardial infarction and its possible mechanism through deacetylase 3/β-catenin/peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. Methods Forty healthy adult male specific pathogen-free SD rats were randomly divided into sham operation group, myocardial infarction group, apigenin group and apigenin +GW9662 (a PPARγ antagonist) group, with 10 rats in each group. Myocardial infarction models were established in all groups except the sham operation group. Then the myocardial infarction group received no other intervention. The apigenin group was intraperitoneally injected with apigenin 5 mg/kg daily for 7 days, and the apigenin +GW9662 group was intraperitoneally injected with GW9662 2 mg/kg daily for 7 days on the basis of the apigenin group. The levels of myocardial enzymes, myocardial morphology, levels of inflammatory factors, apoptosis rate of myocardial cells, and the expression levels of deacetylase 3, β-catenin and PPARγ in myocardial tissue were compared among the groups. Results After the dead rats were removed, 6 rats from each group were randomly selected for each test. The levels of creatine kinase isoenzymes and cardiac troponin I in myocardial infarction group were significantly higher than those in sham operation group(both P<0.001). However, the levels of both in apigenin group were significantly lower than those in myocardial infarction group［(41±6)U/L vs (118±14) U/L, (4.6±1.8)ng/L vs (14.2±2.2)ng/L］(both P<0.001). The levels of both in the apigenin+GW9662 group were significantly higher than those in the apigenin group(both P<0.01). Compared with the myocardial infarction group, the apigenin group had better cell morphology and arrangement, clearer stripes, and less cell necrosis. The levels of interleukin-1β and interleukin-6 in apigenin group were significantly lower than those in myocardial infarction group (both P<0.01), while the levels of interleukin-1β and interleukin-6 in apigenin+GW9662 group were significantly higher than those in apigenin group (both P<0.05). The apoptosis rates of myocardial cells in shamoperation group, myocardial infarction group, apigenin group, and apigenin+GW9662 group were 2.95%, 38.78%, 12.56%, and 22.33%, respectively. The levels of deacetylase 3 and PPARγ in apigenin group were significantly higher than those in myocardial infarction group, and the level of β-catenin was significantly lower in apigenin group than that in myocardial infarction group(all P<0.001). The levels of deacetylase 3 and PPARγ in apigenin +GW9662 group were significantly lower than those in apigenin group(P<0.05 or P<0.01), and the level of β-catenin in apigenin +GW9662 group was significantly higher than that in apigenin group(P<0.05). Conclusion Apigenin can significantly improve cardiac function and reduce cardiomyocyte apoptosis after myocardial infarction by activating deacetylase 3/β-catenin /PPARγ signaling pathway. The protective mechanism of apigenin may involve the regulation of this signaling pathway. Activation of PPARγ is essential for the cardioprotective effects of apigenin.