Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression
Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression
复制标题
DOI：
10.1002/ptr.5787
复制
发表时间：
2017-03-01
影响因子：
7.2
通讯作者：
Zhang, Tao
中科院分区：
文献类型：
--
作者：
Liu, Feng;Huang, Zhuang-Zhuang;Zhang, Tao
冠心舒通胶囊是一种治疗心肌缺血的中药。先前的研究表明，该配方有四种主要活性成分（FMAI），原儿茶酸，隐丹参酮，甘草酸和丁香酚。然而，这些FMAI对MI损伤的作用机制仍不清楚。本研究的目的是评价FMAI在体外和体内对MI的保护作用。体外分离乳鼠心肌细胞，采用MTT法和荧光激活细胞分选仪分别检测细胞活力和凋亡率，并测定细胞内钙离子浓度（[Ca 2 +] i）、钙调素（CaM）和钙调素激酶Ⅱ（CaMK Ⅱ）δ mRNA及蛋白水平。同时用Western blot检测其下游靶蛋白RyR2和PLB的表达。在体内，采用大鼠冠状动脉结扎模型来评估心脏保护作用。检测各组大鼠心脏组织体积及血清肌酸激酶、乳酸脱氢酶、超氧化物歧化酶、谷草转氨酶等生化指标。体外实验结果表明，FMAI可抑制细胞凋亡，降低[Ca 2 +] i，降低CaM和CaMK Ⅱ d的表达，增加RyR2和PLB的表达。在体内，FMAI缩小了梗死面积，降低了肌酸激酶、乳酸脱氢酶和天冬氨酸转氨酶水平，并增强了超氧化物歧化酶活性。总之，我们的数据表明，FMAI抑制钙超载，并发挥其保护作用，通过其抗氧化，抗肿瘤和抗凋亡活动。版权所有（C）2017 JohnWiley & Sons，Ltd.
Guanxin Shutong capsule is a traditional Chinese medicine for the treatment of myocardial ischemia (MI). Previous studies have shown that the formula has four main active ingredients (FMAI), protocatechuic acid, cryptotanshinone, borneol, and eugenol. However, the mechanisms of action of these FMAI against MI injury are still not well known. The aim of the present study was to evaluate the protective effects of the FMAI on MI in vitro and in vivo. In vitro, rat neonatal cardiomyocytes were isolated, the cell viability and apoptosis rate were, respectively, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and fluorescence activating cell sorter, and the intracellular calcium concentration ([Ca2+] i) and CaM and CaMKII delta mRNAas well as protein levels were determined. Meanwhile, their downstreamtargets of RyR2 and PLB were also measured by western blot. In vivo, a rat model of coronary artery ligation was used to evaluate the cardioprotective effects. Infarct sizes of heart tissues and levels of serum biochemical indicators, including creatine kinase, lactate dehydrogenase, superoxide dismutase, and glutamate oxaloacetic transaminase, were measured. The in vitro results showed that the FMAI inhibited cell apoptosis, reduced [Ca2+] i, decreased the expression of CaM and CaMKII d, and increased the expression of RyR2 and PLB. In vivo, the FMAI diminished infract size, reduced creatine kinase, lactate dehydrogenase, and aspartate aminotransferase levels, and enhanced superoxide dismutase activity. In conclusion, our data suggest that the FMAI suppressed calcium overload and exerted its protective effect via its antioxidant, antiinflammatory, and anti-apoptosis activities. Copyright (C) 2017 JohnWiley & Sons, Ltd.