七氟醚预处理可通过上调血管内皮生长因子受体-1发挥心肌保护作用
祝贺贵州医科大学麻醉学院15级科学学位研究生王冬婷顺利毕业
研究方向:麻醉与器官保护 指导老师:高鸿教授
研究生期间共发表文章3篇,其中北图核心2篇
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Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning-mediated cardioprotection
背景与目的
七氟醚预处理(SPC)可以提供类似于缺血预处理的心肌保护作用。 然而其具体机制仍不清楚。之前研究表明血管内皮生长因子受体1(VEGFR-1)参与缺血预处理介导的心肌保护作用。本研究的目的是确定SPC介导的心肌保护作用中VEGFR-1信号传导的重要性。
方 法
采用Langordf离体心脏灌注装置建立大鼠心肌缺血再灌注(I/R)模型。平衡灌注15min后,分别用七氟醚、2.5%七氟醚+MF1 10μmol/L或2.5%七氟醚+胎盘生长因子10μmol/L继续灌注15min后药物脱洗15min,然后缺血30min并再灌注120min。观察血流动力学参数、心肌梗死面积、肌酸激酶MB、乳酸脱氢酶、心肌肌钙蛋白I、肿瘤坏死因子-α、白细胞介素6水平的变化。
结 果
与I/R组相比,2.5%七氟醚预处理可显著改善心功能,缩小心肌梗死面积,减少心肌酶释放,上调VEGFR-1的表达,减少炎症反应。此外,选择性VEGFR-1激动剂及胎盘生长因子并没有增强七氟醚的心肌保护作用和抗炎作用,但特异性VEGFR-1抑制剂MF1则完全阻断了七氟醚的这些效应。
结 论
2.5%七氟醚预处理可减轻心肌I/R损伤,这可能与其抗炎性质和上调VEGFR-1的表达有关。
原始文献摘要
Qian B, Yang Y, Yao Y, Liao Y, Lin Y;Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning-mediated cardioprotection;Drug Des Devel Ther.Apr 6, 2018 ;12:769-776. doi: 10.2147/DDDT.S162577. eCollection 2018.
Purpose: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.
Materials and methods: Myocardial ischemia–reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 μmol/L, or 2.5% sevoflurane+placental growth factor 10 μmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.
Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects.
Conclusion: Our data have demonstrated that 2.5% sevoflurane preconditioning alleviates heart I/R injury, which is probably mediated by the anti-inflammatory property and upregula-tion of VEGFR-1.
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