1.首都医科大学附属北京中医医院心血管科,北京 100010
2.北京市中医药研究所,北京 100010
3.浙江中医药大学中医心脑血管病研究院,杭州 310053
吴彤,女,23岁,硕士研究生。研究方向:中西医结合防治心血管疾病。
仇盛蕾,E-mail: choushenglei@bjzhongyi.com
收稿:2025-01-26,
纸质出版:2025-11-25
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吴彤,仇盛蕾,李思耐,等.心衰合剂对心肌梗死后心力衰竭大鼠PGC-1α/FNDC5信号通路及线粒体动力学的影响[J].北京中医药,2025,44(11):1427-1432.
WU Tong,QIU Shenglei,LI Sinai,et al.Effect of Xinshuai Heji on PGC-1α/FNDC5 signaling pathway and mitochondrial dynamics in rats with heart failure after myocardial infarction[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1427-1432.
吴彤,仇盛蕾,李思耐,等.心衰合剂对心肌梗死后心力衰竭大鼠PGC-1α/FNDC5信号通路及线粒体动力学的影响[J].北京中医药,2025,44(11):1427-1432. DOI: 10.16025/j.1674-1307.2025.11.010.
WU Tong,QIU Shenglei,LI Sinai,et al.Effect of Xinshuai Heji on PGC-1α/FNDC5 signaling pathway and mitochondrial dynamics in rats with heart failure after myocardial infarction[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1427-1432. DOI: 10.16025/j.1674-1307.2025.11.010.
目的
2
探讨心衰合剂(XSHJ)对心肌梗死后心力衰竭(HF)大鼠过氧化物酶体增殖物激活受体γ共激活因子1α/纤维连结蛋白Ⅲ型域包含蛋白5(PGC-1α/FNDC5)信号通路及线粒体动力学的影响。
方法
2
用随机数字表法将大鼠分为假手术组、模型组、阳性对照组及XSHJ低、中、高剂量组。采用结扎大鼠左冠状动脉前降支法建立急性心肌梗死后HF模型,假手术组仅穿线但不结扎。XSHJ低、中、高剂量组分别给予XSHJ 8.75、17.5、35 mg/mL灌胃,均为2 mL/100 g;模型组、假手术组给予等量0.9%氯化钠溶液灌胃;阳性对照组给予曲美他嗪溶液0.5 mg/mL灌胃,2 mL/100 g。自术后1 d起给药,每天灌胃1次,每周5次,共给药4周。采用超声心动仪检测各组大鼠左室射血分数(LVEF)、左室短轴缩短率(FS),用透射电镜观察心肌细胞内线粒体微观结构,用免疫荧光染色(IHC)法检测心肌组织中PGC-1α、FNDC5表达,蛋白免疫印迹法(WB)检测心肌组织中PGC-1α、FNDC5、OPA、Mfn1、Mfn2、Drp1、Fis1蛋白表达,酶联免疫吸附试验(ELISA)检测血清PGC-1α。
结果
2
与模型组比较,各给药组LVEF、FS值高(
P
<
0.05),心肌细胞内线粒体结构损伤减轻,OPA、Mfn1、Mfn2蛋白表达高,Drp1、Fis1蛋白表达低,PGC-1α、FNDC5蛋白表达高(
P
<
0.05),且呈现剂量依赖性。
结论
2
XSHJ可激活心肌梗死后HF大鼠PGC-1α/FNDC5信号通路,抑制心肌细胞线粒体过度分裂,减轻线粒体结构损伤。
Objective
2
To investigate the effects of
Xinshuai Heji
(XSHJ) on the peroxisome proliferator-activated receptor γ coactivator-1α/fibronectin type III domain-containing protein 5 (PGC-1α/FNDC5) signaling pathway and mitochondrial dynamics in rats with post-myocardial infarction heart failure (HF).
Methods
2
Rats were randomly assigned using a random number table into sham operation, model, positive control, and XSHJ low-, medium-, and high-dose groups. The post-myocardial infarction HF model was established by ligation of the left anterior descending coronary artery. Rats in the sham group were only threaded without ligation. The XSHJ low-, medium-, and high-dose groups received XSHJ at 8.75, 17.5, and 35 mg/mL, respectively, by gavage at 2 mL/100 g. The model and sham groups received an equal volume of 0.9% sodium chloride solution, and the positive control group received trimetazidine solution at 0.5 mg/mL, 2 mL/100 g. Administration began 1 day after surgery, once daily, five times per week, for 4 weeks. Echocardiography was used to measure left ventricular ejection fraction (LVEF) and fractional shortening (FS). Transmission electron microscopy observed mitochondrial ultrastructure in myocardial cells. Immunohistochemistry (IHC) detected PGC-1α and FNDC5 expression in cardiac tissue. Western blot (WB) measured protein levels of PGC-1α, FNDC5, OPA, Mfn1, Mfn2, Drp1, and Fis1 in cardiac tissue. ELISA was used to detect serum PGC-1α levels.
Results
2
Compared with the model group, LVEF and FS were significantly increased in all treatment groups (
P
<
0.05). Mitochondrial structural damage in myocardial cells was reduced. Expression levels of OPA, Mfn1, and Mfn2 were increased, while Drp1 and Fis1 were decreased. PGC-1α and FNDC5 protein expression was upregulated (
P
<
0.05) in a dose-dependent manner.
Conclusion
2
XSHJ can activate the PGC-1α/FNDC5 signaling pathway in rats with post-myocardial infarction HF, inhibit excessive mitochondrial fission in myocardial cells, and reduce mitochondrial structural damage.
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