吉林大学学报(医学版) ›› 2020, Vol. 46 ›› Issue (04): 792-797.doi: 10.13481/j.1671-587x.20200420

• 基础研究 • 上一篇    

舒芬太尼后处理通过ERK1/2介导的p70S6K信号通路对大鼠心肌缺血再灌注损伤的保护作用

闻颖1, 吴巧玲2, 刘国利2   

  1. 1. 锦州医科大学研究生学院, 辽宁 锦州 121000;
    2. 锦州医科大学附属第一医院麻醉科, 辽宁 锦州 121000
  • 收稿日期:2019-11-24 发布日期:2020-08-20
  • 通讯作者: 刘国利,教授,主任医师,硕士研究生导师(Tel:0416-4197484,E-mail:liuguoli1960@163.com) E-mail:liuguoli1960@163.com
  • 作者简介:闻颖(1986-),女,辽宁省葫芦岛市人,在读医学硕士,主要从事临床麻醉学方面的研究。
  • 基金资助:
    辽宁省科技厅自然科学基金指导项目资助课题(20180550806)

Protective effect of sufentanil post-conditioningthrough ERK1/2-mediated p70S6K signaling pathway on myocardial ischemia-reperfusion injuryof rats

WEN Ying1, WU Qiaoling2, LIU Guoli2   

  1. 1. Graduate School, Jinzhou Medical University, Jinzhou 121000, China;
    2. Department of Anesthesiology, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China
  • Received:2019-11-24 Published:2020-08-20

摘要: 目的:探讨舒芬太尼后处理通过细胞外调节蛋白激酶1/2(ERK1/2)介导的p70核糖体蛋白S6激酶(p70S6K)信号传导通路对大鼠心肌缺血再灌注损伤(MIRI)的影响,阐明舒芬太尼后处理对大鼠MIRI的保护作用。方法:72只SD雄性大鼠随机分为假手术组、缺血再灌注(I/R)组、二甲基亚砜(DMSO)组、PD组(缺血末到再灌注开始后15min给予20 μmol·L-1ERK的抑制剂PD98059)、舒芬太尼后处理组(Sufen组)和Sufen+PD组。除假手术组外,其余各组大鼠均缺血30min后再灌注2 h。于缺血前即刻(T0)和再灌注30min(T1)、60min(T2)、90 min(T3)、2h(T4)时记录心率(HR)、平均动脉压(MAP),再灌注末测定大鼠心肌梗死面积,采用Western blotting法检测大鼠心肌组织中p-ERK1/2和p-p70S6K蛋白表达水平。结果:与T0时比较,T1~T4时I/R组、Sufen组、DMSO组、PD组和PD+Sufen组大鼠MAP和HR降低(P<0.05);与假手术组比较,其余各组大鼠HR降低(P<0.05),MAP升高(P<0.05);与I/R组比较,T3时Sufen组大鼠HR降低(P<0.05),MAP升高(P<0.05)。与I/R组比较,Sufen组大鼠心肌梗死面积明显减少(P<0.05);与Sufen组比较,PD+Sufen组大鼠心肌梗死面积明显增加(P<0.05)。与假手术组比较,I/R组、Sufen组和DMSO组大鼠心肌组织中p-ERK1/2和p-p70S6K蛋白表达水平均明显升高(P<0.05);与I/R组比较,Sufen组大鼠心肌组织中p-ERK1/2和p-p70S6K蛋白表达水平均进一步升高(P<0.05);与Sufen组比较,PD+Sufen组大鼠心肌组织中的p-ERK1/2和p-p70S6K蛋白表达水平均明显降低(P<0.05)。结论:舒芬太尼后处理通过ERK1/2介导的p70S6K信号通路对大鼠MIRI起保护作用,可改善MIRI大鼠的心功能指标,减少心肌梗死面积。

关键词: 舒芬太尼, 缺血再灌注损伤, 细胞外调节蛋白激酶1/2, p70核糖体蛋白S6激酶, 心肌梗死

Abstract: Objective: To investigate the effect of sufentanil post-conditioning on the myocardial ischemia reperfusion injury (MIRI) through extracellular regulated protein kinases (ERK1/2)-mediated p70S6K signaling pathway in the rats, and to clarify the protective effect of sufentanil post-conditioning on the MIRI of the rats. Methods: Seventy-two male SD rats were randomly divided into sham operation group, ischemia-reperfusion group (I/R group), dimethylsulfoxide group (DMSO group), PD group (an inhibitor of ERK, 20 μmol·L-1 PD98059 was administered 15 min after the end of ischemia to the start of reperfusion), sufentanil post-conditioning group (Sufen group), Sufen+PD group. Except for sham operation group, the rats in other groups were reperfused for 2 h after 30 min-ischemia. The heart rates (HR) and mean artery pressures (MAP) of the rats in various goups were recorded immediately before ischemia (T0), 30 min of ischemia (T1), 30 min of reperfusion (T2), 60 min of reperfusion (T3), 90 min of reperfusion (T4), and 120 min (T5). The myocardial infarction area was measured at the end of reperfusion; the expression levels of p-ERK1/2 and p-p70S6K proteins in myocardium tissue were detected by Western blotting method. Results: Compared with T0, The MAP and HR of the rats in I/R, Sufen, DMSO, PD, and PD + Sufen groups at T1-T4 were decreased (P<0.05).Compared with sham operation group, the HR and MAP of the rats in other groups were increased(P<0.05). Compared with I/R group, the HR and MAP of the rats in Sufen group were increased (P<0.05).Compared with I/R group (45.67% ±10.32%), the myocardial infarct area of the rats in Sufen group (20.92% ±6.88%) was reduced (P<0.05).Compared with Sufen group, the myocardial infarction area in PD + Sufen group (42.14% ±6.73%) was increased (P<0.05). Compared with sham operation group, the expression levels of p-ERK1/2and p-p70S6K proteints in myocardium tissue of the rats in I/R group, Sufen group, and DMSO group were increased (P<0.05).Compared with I/R group, the expression levels of p-ERK1/2 and p-p70S6K in myocardium tissue of the rats in Sufen group were further increased(P<0.05).Compared with Sufen group, the expression levels of p-ERK1/2 and p-p70S6K proteins in myocardium tissue of the rats in PD+Sufen group were decreased(P<0.05). Conclusion: Sufentanil post-conditioning has the protective effect on MIRI in the rats through ERK1/2-mediated p70S6K signaling pathway. Sufentanil post-conditioning improves the cardiac function indicators and reduces the myocardial infarction area.

Key words: sufentanil, ischemia-reperfusion injury, extracellular-signal regulated kinase1/2, ribosomal protein S6 kinase, myocardial infarction

中图分类号: 

  • R971.2