Wang Lixin, Ma Hao, Xue Yan, Shi Haiyan, Ma Teng, Cui Xiaozheng
Department of Cardiovascular Surgery, The General Hospital of The Chinese People's Armed Police Forces, Beijing 100039, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1225-1232. doi: 10.3892/etm.2017.5575. Epub 2017 Nov 27.
Myocardial ischemia-reperfusion injury is one of the most common cardiovascular diseases, and can lead to serious damage and dysfunction of the myocardial tissue. Previous studies have demonstrated that berberine exhibits ameliorative effects on cardiovascular disease. The present study further investigated the efficacy and potential mechanism underlying the effects of berberine on ischemia-reperfusion injury in a mouse model. Inflammatory markers were measured in the serum and levels of inflammatory proteins in myocardial cells were investigated after treatment with berberine. In addition, the apoptosis of myocardial cells was investigated after berberine treatment. Apoptosis-associated gene expression levels and apoptotic signaling pathways were analyzed in myocardial cells after treatment with berberine. The phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) and nuclear factor (NF)-κB signaling pathways were also analyzed in myocardial cells after treatment with berberine. Histological analysis was used to analyze the potential benefits of berberine in ischemia-reperfusion injury. The present study identified that inflammatory responses and inflammatory factors were decreased in the myocardial cells of the mouse model of ischemia-reperfusion injury. Mechanism analysis demonstrated that berberine inhibited apoptotic protease-activating factor 1, caspase-3 and caspase-9 expression in myocardial cells. The expression of Bcl2-associated agonist of cell death, Bcl-2-like protein 1 and cellular tumor antigen p53 was upregulated. Expression of NF-κB p65, inhibitor of NF-κB kinase subunit β (IKK-β), NF-κB inhibitor α (IκBα), and NF-κB activity, were inhibited in myocardial cells in the mouse model of ischemia-reperfusion injury. In conclusion, the results of the present study indicate that berberine inhibits inflammatory responses through the NF-κB signaling pathway and suppresses the apoptosis of myocardial cells via the PI3K/AKT signaling pathway in a mouse model of ischemia-reperfusion injury. These results suggest that berberine is a potential drug for the treatment of patients with ischemia-reperfusion injury.
心肌缺血再灌注损伤是最常见的心血管疾病之一，可导致心肌组织严重损伤和功能障碍。先前的研究表明，黄连素对心血管疾病具有改善作用。本研究进一步探讨了黄连素对小鼠缺血再灌注损伤的疗效及潜在作用机制。在用黄连素治疗后，检测血清中的炎症标志物，并研究心肌细胞中炎症蛋白的水平。此外，还研究了黄连素治疗后心肌细胞的凋亡情况。分析了黄连素处理后心肌细胞中凋亡相关基因表达水平及凋亡信号通路。还分析了黄连素处理后心肌细胞中的磷酸肌醇3激酶（PI3K）/RAC-α丝氨酸/苏氨酸蛋白激酶（AKT）和核因子（NF）-κB信号通路。采用组织学分析来分析黄连素在缺血再灌注损伤中的潜在益处。本研究发现，缺血再灌注损伤小鼠模型的心肌细胞中炎症反应和炎症因子减少。机制分析表明，黄连素抑制心肌细胞中凋亡蛋白酶激活因子1、半胱天冬酶-3和半胱天冬酶-9的表达。细胞死亡的Bcl2相关激动剂、Bcl-2样蛋白1和细胞肿瘤抗原p53的表达上调。在缺血再灌注损伤小鼠模型的心肌细胞中，NF-κB p65、NF-κB激酶亚基β（IKK-β）、NF-κB抑制剂α（IκBα）的表达及NF-κB活性均受到抑制。总之，本研究结果表明，在缺血再灌注损伤小鼠模型中，黄连素通过NF-κB信号通路抑制炎症反应，并通过PI3K/AKT信号通路抑制心肌细胞凋亡。这些结果表明黄连素是治疗缺血再灌注损伤患者的一种潜在药物。
