神经调节蛋白1/表皮生长因子受体4信号通路的激活加强了七氟醚对心肌缺血/再灌注损伤大鼠的心肌保护作用

Enhanced cardioprotective effect of sevoflurane on myocardial ischemia/reperfusion injury in rats through the activation of Neuregulin 1/receptor tyrosine-protein kinase erbB-4 signaling pathway

目的研究七氟醚预处理中神经调节蛋白1(NRG1)/表皮生长因子受体4(Erb B4)信号通路的激活对大鼠在体心肌缺血/再灌注损伤(I/R)的保护作用。方法按照体重将SD大鼠随机分为5组,每组10只:假手术组、模型组、七氟醚组、七氟醚+NRG1类似物组、七氟醚+NRG1类似物+AG1478组。其中,40只大鼠在给药后制备I/R模型,30只给予2.4%七氟醚麻醉处理,20只腹腔注射NRG1类似物,10只腹腔注射NRG1类似物+AG1478。用缺口末端标记法检测心肌凋亡情况;以免疫印迹检测Erb B4/p-Erb B4蛋白表达;以酶联免疫吸附法检测NRG1表达。结果假手术组、模型组、七氟醚组、七氟醚+NRG1类似物组、七氟醚+NRG1类似物+AG1478组的细胞凋亡指数分别为1.10±0.03,32.82±6.43,12.38±2.25,6.23±1.88,14.87±2.28。这5组的NRG1含量分别为178.3±20.8,92.3±16.5,120.4±18.2,151.6±20.7,149.1±18.7;这5组的p-Erb B4/Erb B4表达水平分别为0.81±0.08,0.42±0.05,0.60±0.08,0.72±0.07,0.61±0.09。上述指标:模型组与假手术组相比,差异均有统计学意义(均P<0.05);3个给药组与模型组相比,差异均有统计学意义(均P<0.05)。结论激活NRG1/Erb B4信号通路进一步加强了七氟醚对心肌的保护作用。

Objective To investigate the cardioprotection effect of sevoflurane on myocardial ischemia/reperfusion injury（ IR） in rats by activating neuregulin 1（ NRG1）/receptor tyrosine-protein kinase erb B-4（ Erb B4） signaling pathway. Methods Among fifty Sprague-Dawley（ SD） rats,10 rats underwent sham operation and the remaining 40 rats were prepared for IR modeling. Before IR modeling,30 rats received the treatment of 2. 4% sevoflurane and 20 of them then were treated by NRG1-β1（ the NRG1 mimic） and a combination of NRG1-β1 and AG1478（ the Erb B4 inhibitor） respectively. Apoptotic cells were defined by Td T-mediated d UTP nick-end labeling. The Erb B4 and p-Erb B4 expressions were detected by Western blot. The NRG1 expression was determined by enzyme-linked immunosorbent assay. Results The apoptotic indexes in sham operation group,model group,sevoflurane group,sevoflurane ＋ NRG1 analog group,sevoflurane ＋ NRG1 analog ＋ AG1478 group were 1. 10 ± 0. 03,32. 82 ± 6. 43,12. 38 ± 2. 25,6. 23 ± 1. 88,14. 87 ± 2. 28. The NRG1 contents in the 5 groups were 178. 3 ± 20. 8,92. 3 ± 16. 5,120. 4 ± 18. 2,151. 6 ± 20. 7,149. 1 ± 18. 7. The expression levels of p-Erb B4/Erb B4 in the 5 groups were0. 81 ± 0. 08,0. 42 ± 0. 05,0. 60 ± 0. 08,0. 72 ± 0. 07,0. 61 ± 0. 09. Comparison sham operation group with model group showed that the factors had statistically significant differences（ all P 0. 05）; by comparison 3 drugs groups with model group,it was found that the factors had statistically significant differences（ all P 0. 05）. Conclusion Activation of the NRG1/Erb B4 signaling pathway strengthens the protective effect of sevoflurane on myocardium.