羟基红花黄素A对缺血性心力衰竭大鼠心肌自噬及ERK1/2通路的影响
Effects of hydroxysafflor yellow A on myocardial autophagy and ERK1/2 pathway in rats with ischemic heart failure

崔云云等.羟基红花黄素A对缺血性心力衰竭大鼠心肌自噬及ERK1/2通路的影响[J].内科急危重症杂志,2020,26(3):221-225

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DOI：10.11768/nkjwzzzz20200312

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基金项目:四川省科技攻关项目（No:2017JY0260)

作者	单位	E-mail
崔云云等	西宁市第二人民医院	zwqv99@163.com

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中文摘要:

目的:探讨羟基红花黄素A（HSYA）对缺血性心力衰竭（IHF）大鼠心肌自噬及细胞外调节蛋白激酶(ERK1/2)通路的影响。方法:将72只大鼠随机分为假手术组、模型组、阳性对照组（卡托普利组）、低剂量HSYA组（L-HSYA）、中剂量HSYA组（M-HSYA）、高剂量HSYA组（H-HSYA），每组12只。采用冠脉结扎法建立缺血性心力衰竭大鼠模型。超声仪检测大鼠左心室心功能水平，酶联免疫吸附法（ELISA）检测血清N-末端脑钠肽前体（NT-proBNP）和超敏肌钙蛋白（hs-TnT)水平，透射电镜观察心肌细胞自噬，Western blot法检测心肌组织自噬相关因子微管相关蛋白1（Beclin1）、微管相关蛋白轻链3（LC3)、泛素和LC3结合蛋白p62（p62)、ERK1/2蛋白表达。结果:与模型组比较，阳性对照组、M-HSYA和H-HSYA组大鼠左室收缩末期室间隔厚度（LVSs）、左室舒张末期室间隔厚度（LVSd）、收缩末期左心室后壁厚度（ LVPWs）、舒张末期左心室后壁厚度（LVPWd）、左心室射血分数（LVEF）及L-〖JP2〗HSYA组LVSd显著升高（均P＜0.05）；心电图T波幅度和ST段抬高幅度显著降低，QT间期显著缩短（均P＜0.05）；大鼠血清NT-proBNP和hs-TnT水平显著降低（均P＜0.05），心肌细胞自噬小体数量减少，自噬率显著降低（P＜0.05）；心肌组织Beclin-1、LC3Ⅰ、LC3Ⅱ蛋白表达显著降低（均P＜0.05），p62和p-ERK1/2蛋白表达显著升高（均P＜0.05）。结论：IHF大鼠心肌损伤与自噬关系密切，HSYA可能通过激活ERK1/2信号通路抑制IHF大鼠心肌细胞自噬。

英文摘要:

Objective: To investigate the effect of hydroxysafflor yellow A (HSYA) on myocardial autophagy and extracellular regulated protein kinase (ERK1/2) pathway in rats with ischemic heart failure (IHF). Methods: Seventy-two rats were randomly divided into sham operation group, model group, positive control group (captopril group), low-dose HSYA (L-HSYA) group, medium-dose HSYA (M-HSYA) group and high-dose HSYA (H-HSYA) group, with 12 rats in each group. The rat model of IHF was established by ligation of coronary artery. The left ventricular function of rats was measured by echocardiography, enzyme-linked immunosorbent assay (ELISA) was used to detect serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT) contents, the autophagy of myocardial cells was observed by transmission electron microscopy, and Western blotting was used to detect the expression of autophagy related factor microtubule associated protein 1 (Beclin 1), microtubule associated protein light chain 3 (LC3), ubiquitin and LC3 binding protein p62 (p62) and ERK1/2 in myocardium. Results: Compared with model group, the left ventricular interventricular septal thickness during systole (LVSs), left ventricular interventricular septal thickness during diastole(LVSd), left ventricular posterior wall thickness at end-systole(LVPWs), left ventricular posterior wall depth(LVPWd) and left ventricular fraction(LVEF) in positive control group, M-HSYA and H-HSYA groups and LVSd in L-HSYA group increased significantly (all P<0.05); the T wave amplitude and ST segment elevation amplitude of ECG were 〖JP2〗significantly decreased, and the QT interval was significantly shortened (all P<0.05); the contents of NT-proBNP and hs-TNT in serum of rats decreased significantly (all P<0.05), the number of autophagic bodies in cardiomyocytes decreased, and the autophagy rate decreased significantly (all P<0.05), the expression of Beclin-1, LC3Ⅰ and LC3 Ⅱ in myocardial tissues was significantly decreased, and the expression of p62 and p-ERK1/2 significantly increased (all P<0.05). Conclusion: Myocardial injury is closely related to autophagy in IHF rats. HSYA may reduce the autophagy of myocardial cells in IHF rats by activating ERK1/2 signaling pathway.