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目的:明确Notch1通路在高温高湿条件下小鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤中的作用及其潜在机制。方法:将成年C57小鼠随机分为(1)假手术组;(2)I/R组;(3)高温高湿组;(4)高温高湿+I/R组;(5)高温高湿+Jagged1(Notch1激动剂)+I/R组;(6)高温高湿+溶剂+I/R组。采用超声心动图检测心功能,伊文氏蓝/2,3,5-三苯基氯化四氮唑双染法检测心肌梗死面积,Western blot检测Notch1细胞内段(Notch1 intracellular domain,Notch1 ICD)、Hairy和分裂增强子(Hairy and enhancer of split,Hes1)、微管相关蛋白1轻链3(microtubule-associated protein1 light chain 3,LC3)、Beclin1和p62的蛋白表达水平。结果:与假手术组对比,I/R组心功能下降,心肌梗死面积增加,Notch1 ICD、Hes1、LC3-Ⅱ/Ⅰ、Beclin1(p62相应降低)表达升高,而高温高湿组心功能下降,心肌梗死面积增加,Notch1 ICD、Hes1、LC3-Ⅱ/Ⅰ、Beclin1(p62相应升高)表达降低;和I/R组或高温高湿组对比,高温高湿+I/R组心功能进一步下降,心肌梗死面积进一步增加,Notch1 ICD、Hes1、LC3-Ⅱ/Ⅰ、Beclin1(p62进一步升高)表达进一步降低;和高温高湿+I/R组对比,加入Notch1激动剂Jagged1后,心功能提高,心肌梗死面积缩小,Notch1 ICD、Hes1、LC3-Ⅱ/Ⅰ、Beclin1(p62相应降低)表达升高。结论:激活Notch1通路可能通过促进自噬从而缓解高温高湿所致的心肌缺血/再灌注损伤。
Objective: To investigate the role of Notch1 pathway in myocardial ischemia / reperfusion (I / R) injury induced by high temperature and high humidity and its potential mechanism. Methods: Adult C57 mice were randomly divided into (1) sham operation group, (2) I / R group, (3) high temperature and high humidity group, (4) high temperature and high humidity + I / R group, Wet + Jagged1 (Notch1 agonist) + I / R group; (6) high temperature and high humidity + solvent + I / R group. The heart function was detected by echocardiography, the area of myocardial infarction was detected by Evans blue / 2,3,5-triphenyltetrazolium chloride staining, and the Notch1 intracellular domain (Notch1 ICD) Hairy and enhancer of split (Hes1), microtubule-associated protein1 light chain 3 (LC3), Beclin1 and p62. Results: Compared with the sham operation group, the cardiac function of I / R group was decreased and the area of myocardial infarction was increased. The expression of Notch1 ICD, Hes1, LC3-Ⅱ / Ⅰ and Beclin1 (p62 decreased accordingly) , Myocardial infarction area increased, Notch1 ICD, Hes1, LC3-Ⅱ / Ⅰ, Beclin1 (p62 correspondingly increased) expression decreased; Compared with I / R group or high temperature and humidity group, Decreased, myocardial infarction area further increased, Notch1 ICD, Hes1, LC3-Ⅱ / Ⅰ, Beclin1 (p62 further increased) expression further reduced; and high temperature and humidity + I / R group compared with the addition of Notch1 agonist Jagged1, Increased myocardial infarct size, Notch1 ICD, Hes1, LC3-Ⅱ / Ⅰ, Beclin1 (p62 corresponding decrease) increased expression. Conclusion: Activation of Notch1 pathway may relieve myocardial ischemia / reperfusion injury induced by high temperature and high humidity by promoting autophagy.