Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China.
The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China.
Phytomedicine. 2018 Mar 15;42:18-24. doi: 10.1016/j.phymed.2018.03.014. Epub 2018 Mar 7.
Injection of snakegourd peel (SP), an herb used in traditional Chinese medicine, is used to treat coronary artery disease and stable angina in China. However, its therapeutic role and mechanism of action for the treatment of myocardial infarction (MI) is not fully understood.
The present study was designed to investigate the effect of SP on MI-induced cardiac injury and elucidate its underlying molecular mechanisms.
To create an in vivo model of MI, we ligated the left coronary artery of Wistar rats. For our in vitro model of MI, we treated primary neonatal rat ventricular myocytes with hypoxia. Myocardial infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Intracellular calcium concentration (Ca) was measured by confocal microscopy, and cardiomyocyte apoptosis was assessed by TUNEL assay. Western blot was applied to determine protein levels.
Three days post-MI, SP significantly improved MI-induced impairment of cardiac function, as indicated by increased left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure rise and fall (± dp/dt max), and decreased left ventricular end-diastolic pressure (LVEDP). In addition, SP treatment markedly reduced the infarct size and serum lactate dehydrogenase (LDH) activity; inhibited cardiomyocyte apoptosis and Caspase-3 activation both in vivo and in vitro; and decreased intracellular calcium overload, Cav1.2, phosphorylated JNK (p-JNK), and p38 MAPK (p-p38 MAPK) levels in ischemic myocardium.
SP alleviated cardiac ischemic injury and inhibited cardiomyocyte apoptosis by attenuating intracellular calcium overload, suppressing Caspase-3 activation, and downregulating protein expression of p-JNK and p-p38MAPK. These results suggest that SP may serve as a potential novel therapeutic drug for MI.
中药葫芦素注射液用于治疗冠心病和稳定型心绞痛。然而,其治疗心肌梗死(MI)的作用机制尚不完全清楚。
本研究旨在探讨葫芦素注射液对 MI 诱导的心肌损伤的作用及其潜在的分子机制。
结扎 Wistar 大鼠左冠状动脉以建立体内 MI 模型,用缺氧处理原代新生大鼠心室肌细胞以建立体外 MI 模型。通过氯化三苯基四氮唑(TTC)染色测量心肌梗死面积。通过共聚焦显微镜测量细胞内钙离子浓度(Ca2+),通过 TUNEL 检测评估心肌细胞凋亡。应用 Western blot 测定蛋白水平。
MI 后 3 天,葫芦素注射液显著改善了 MI 引起的心脏功能障碍,表现为左心室收缩压(LVSP)升高、左心室压力最大上升和下降速率(±dp/dt max)升高、左心室舒张末期压力(LVEDP)降低。此外,葫芦素注射液治疗明显减小了梗死面积和血清乳酸脱氢酶(LDH)活性;在体内和体外均抑制了心肌细胞凋亡和 Caspase-3 的激活;并降低了缺血心肌细胞内钙离子超载、Cav1.2、磷酸化 JNK(p-JNK)和磷酸化 p38MAPK(p-p38MAPK)水平。
葫芦素注射液通过减轻细胞内钙超载、抑制 Caspase-3 激活和下调 p-JNK 和 p-p38MAPK 蛋白表达,减轻了心肌缺血损伤,抑制了心肌细胞凋亡。这些结果表明,葫芦素注射液可能成为治疗 MI 的一种有潜力的新型治疗药物。