Suchal Kapil, Malik Salma, Gamad Nanda, Malhotra Rajiv Kumar, Goyal Sameer N, Bhatia Jagriti, Arya Dharamvir Singh
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra-425405, India.
Phytomedicine. 2016 Nov 15;23(12):1401-1408. doi: 10.1016/j.phymed.2016.07.015. Epub 2016 Aug 4.
Myocardial infarction (MI) continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Kaempferol (KMP), a dietary flavonoid, possesses good antioxidant, immunomodulatory and anti-apoptotic properties and has been evaluated in the present study for its role in mitigating myocardial injury following MI.
In this study, the ability of KMP to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated.
Male Wistar rats (n=48) were administered KMP (5, 10 & 20mg/kg/day, i.p.) or vehicle for 15 days with ISO, 85mg/kg, subcutaneously, for 2 consecutive days was also administered at 24h interval on the 13th and 14th days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Later on blood sample was collected and heart was removed to estimate biochemical, histopathological, ultrastructural and immuohistochemical studies respectively.
ISO-treated rats showed a significant reduction in arterial pressure, maximum rate of development of left ventricular pressure and increase in left ventricular end-diastolic pressure. Also, there was a significant decrease in antioxidant enzyme levels such as superoxide dismutase, catalase and glutathione and increase in the level of malondialdehyde and serum TNF-α and IL-6 levels. In addition, the cardiac injury markers such as creatine kinase-MB and lactate dehydrogenase were increased in the serum. Furthermore, immunohistochemistry revealed an increased Bax/Bcl-2 ratio in the myocardium. KMP (5, 10 and 20mg/kg) dose dependently restored hemodynamic, left ventricular functions, decreased cardiac injury marker enzymes in serum, increased antioxidant levels, reduced lipid peroxidation and TNF-α level and apoptosis. Histopathological and ultrastructural studies support the protective effect of KMP in ISO-induced myocardial infarcted rats.
Thus, the present study revealed that KMP mitigates myocardial damage in ISO-induced cardiac injury by maintaining hemodynamic and biochemical parameters and reducing inflammation owing to its anti-apoptotic, anti-inflammatory and antioxidant activities. It may be concluded that a diet containing KMP may be beneficial in those who are at the risk of myocardial injury.
尽管现有治疗方法可用，但心肌梗死（MI）在全球范围内仍然与高发病率和死亡率相关。山奈酚（KMP）是一种膳食黄酮类化合物，具有良好的抗氧化、免疫调节和抗凋亡特性，本研究对其在减轻心肌梗死后心肌损伤中的作用进行了评估。
本研究评估了KMP保护心脏免受异丙肾上腺素（ISO）诱导的氧化应激和心肌梗死的能力。
雄性Wistar大鼠（n = 48）给予KMP（5、10和20mg/kg/天，腹腔注射）或赋形剂，持续15天，在第13天和第14天每隔24小时皮下注射ISO 85mg/kg，连续2天。在第15天，将大鼠麻醉并插入右冠状动脉以记录血流动力学参数。随后采集血样并取出心脏，分别进行生化、组织病理学、超微结构和免疫组织化学研究。
ISO处理的大鼠动脉压、左心室压力最大上升速率显著降低，左心室舒张末期压力升高。此外，超氧化物歧化酶、过氧化氢酶和谷胱甘肽等抗氧化酶水平显著降低，丙二醛水平以及血清TNF-α和IL-6水平升高。另外，血清中心肌损伤标志物如肌酸激酶-MB和乳酸脱氢酶升高。此外，免疫组织化学显示心肌中Bax/Bcl-2比值增加。KMP（5、10和20mg/kg）剂量依赖性地恢复了血流动力学、左心室功能，降低了血清中心肌损伤标志物酶水平，提高了抗氧化水平，减少了脂质过氧化和TNF-α水平以及细胞凋亡。组织病理学和超微结构研究支持KMP对ISO诱导的心肌梗死大鼠的保护作用。
因此，本研究表明，KMP通过维持血流动力学和生化参数以及因其抗凋亡、抗炎和抗氧化活性减轻炎症，从而减轻ISO诱导的心脏损伤中的心肌损伤。可以得出结论，含有KMP的饮食可能对有心肌损伤风险的人有益。
