摘要
目的:研究中药复方制剂丹红注射液对冠脉结扎大鼠心肌细胞凋亡的影响及相关分子机制。方法:取40只雄性Sprague-Dawley(SD)大鼠随机分为假手术组、模型组、丹红注射液低、中、高剂量组,左前降支冠状动脉结扎法造成急性心梗模型,采用超声心动图法记录大鼠心功能,TUNEL标记法检测心肌组织细胞凋亡状况,蛋白免疫印迹法检测心肌组织B细胞淋巴瘤/白血病-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)的表达、天冬氨酸蛋白水解酶-3(Caspase-3)的活化、Janus激酶2(Janus kinase 2,JAK2)和信号转导及转录激活因子3(signal transducer and activator of transcription 3, STAT3)的磷酸化水平。结果:丹红注射液能剂量依赖性地升高大鼠心功能指标左室射血分数(left ventricular ejection fraction, LVEF)和左室短轴缩短率(left ventricular fractional shortening, LVFS)的值,减少缺血损伤诱导的心肌细胞凋亡,增加抗凋亡基因Bcl-2的表达,减少促凋亡基因Bax的表达及Caspase-3的活化,并上调JAK2和STAT3的磷酸化水平。结论:丹红注射液可显著改善大鼠心功能,抑制缺血诱导的心肌细胞凋亡,其机制可能与调节凋亡相关基因及JAK2/STAT3信号通路参与调控有关。
Objective: To investigate the effects ofDanhong injection(DHI) on cardiomyocyte apoptosisand related molecular mechanismsin rats with myocardial infarction(MI). Methods: 40 male Sprague-Dawleyrats were randomly divided into five groups:Sham-operated group;MI+ saline group;MI+ DHI 0.5 m L/kg group;MI+ DHI 1 mL/kg group;MI+ DHI 2 mL/kg group, and acuteMIwere induced by ligation of left anteriordescending coronary artery. After intravenous injection for 7 days, the cardiac function of ratswasassessed by echocardiography. Then the cardiomyocyte apoptosis index was detected by terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) technology, and the expression of B-cell lymphoma/lewkmia-2(Bcl-2), Bcl-2 associated X protein(Bax), Cleaved cysteine aspartate protease-3(Caspase-3), and phosphorylation levels of Januskinase 2(JAK2) and signal transducerand activator of transcription 3(STAT3)inmyocardiumwere determined by western blot analysis. Results: DHI restored cardiac function evidenced by increases of left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)in a dose-dependent manner, and inhibited cardiomyocytes apoptosis induced by ischemia injury. Furthermore, DHI increased Bcl-2 expression, while decreased Bax and active caspase-3 expression. The phosphorylation of JAK2/STAT3 was also upregulated by DHI. Conclusion: DHI couldsignificantly improve left ventricular function of MI rats, and inhibit ischemia-induced cardiomyocytes apoptosis. These beneficial effects may be associated with the regulation of apoptosis related gene and JAK2/STAT3 signal pathway.
作者
殷英
卫国
段佳林
王艳华
翁琰
郭超
文爱东
YIN Ying;WEI Guo;DUAN Jia-lin;WANG Yan-hua;WENG Yan;GUO Chao;WEN Ai-dong(Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi'an,Shaanxi,710032,China)
出处
《现代生物医学进展》
CAS
2019年第11期2051-2055,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81403135)
