文章摘要
黄檀素对心肌缺血/再灌注损伤的治疗作用及机制研究
Role of activation of Dalbergin in inhibiting myocardial ischemia/ reperfusion injury in mice
投稿时间:2020-09-29  修订日期:2020-09-29
DOI:
中文关键词: 黄檀素  心肌缺血/再灌注损伤  心肌细胞  心脏功能
英文关键词: Dalbergin  Myocardial ischemia/reperfusion injury  Cardiomyocytes  Heart function
基金项目:国家自然科学基金(81903837);陕西省科技厅项目(2018SF-129);西安医学院第二附属医院院级课题(19KY0113)
作者单位E-mail
王军 武警陕西省总队医院麻醉科 396744196@qq.com 
邵治泓 空军军医大学第一附属医院 zhaomeina1211@163.com 
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中文摘要:
      目的:探讨黄檀素(DAL)对小鼠心肌缺血/再灌注(MI/R)损伤心肌的保护作用及其作用机制。 方法:选择成年雄性C57 BL/6J小鼠随机分为假手术组(Sham)、模型组(MI/R)、地尔硫组(Diltiazem)和DAL低、中、高剂量组(10、30、90 mg/kg/d)组,每组10只。结扎小鼠冠状动脉左前降支(LAD),缺血30 min,再灌注1 h建立小鼠MI/R损伤模型。术后第1天起,假手术组、模型组小鼠均灌胃等体积生理盐水,DAL各剂量组小鼠灌胃相应药液,每日1次,连续7 d。给药结束后检测小鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)活性及肿瘤坏死因-α(TNF-α)、白细胞介素-6(IL-6)含量;检测小鼠心肌组织中超氧化歧化酶(SOD)活性和丙二醛(MDA)含量;苏木精-伊红染色(HE)检测心肌损伤病理形态;Western Blot检测心肌组织中Akt和P-Akt的蛋白水平表达变化;超声检测左室舒张末内径(ESD)、左室舒张末容积(EDV)、射血分数(EF)和短轴缩短率(FS)。 结果:DAL可以减轻小鼠血清中CK-MB、LDH活性及TNF-α、IL-6含量;升高小鼠心肌组织中SOD活性,减少MDA生成;增加p-Akt 的蛋白水平表达,减轻心肌组织病理损伤,改善心脏功能。 结论:DAL可通过增加Akt磷酸化促进心肌细胞存活进而抑制心肌缺血/再灌注损伤,最终发挥心肌保护作用。
英文摘要:
      Objective: To explore the protective effect of Dalbergin (DAL) on myocardial ischemia/reperfusion (MI/R) injury in mice and its mechanism. Methods: Adult male C57 BL/6J mice were randomly divided into sham operation group, model group, diltiazem group, DAL low, medium, and high dose groups (10, 30, 90 mg/kg/d), with 10 mice in each group. The mouse left anterior descending coronary artery (LAD) was ligated, ischemia for 30 minutes, and reperfusion for 1 hour to establish a mouse MI/R injury model. From the first day after the operation, mice in the sham operation group and model group were intragastrically administered with equal volume of normal saline, and mice in each dose group of DAL were intragastrically administered with the corresponding liquid once a day for 7 consecutive days. After the administration, the creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum of mice were detected ) Content; detection of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in mouse myocardial tissue; hematoxylin-eosin staining (HE) detection of myocardial injury pathology; Western Blot detection of Akt and P in myocardial tissue -Akt protein level expression changes; ultrasound detection of left ventricular end diastolic diameter (ESD), left ventricular end diastolic volume (EDV), ejection fraction (EF) and short axis shortening rate (FS). Results: DAL can reduce the activity of CK-MB and LDH and the content of TNF-α and IL-6 in the serum of mice; increase the activity of SOD in mouse myocardial tissue and reduce the production of MDA (P <0.01 or P <0.05); increase the expression of p-Akt protein, reduce pathological damage of myocardial tissue, and improve cardiac function. Conclusions: DAL can promote the survival of cardiomyocytes by increasing Akt phosphorylation, thereby inhibiting myocardial ischemia/reperfusion injury, and finally play a role in myocardial protection.
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