摘要
目的观察神经调节因子1(NRG1)-ErbB4信号通路在脓毒症大鼠心肌功能障碍中的作用。方法成年雄性SD大鼠40只随机均分为对照组、脂多糖(LPS)组、LPS+重组NRG1(rhNRG1)组和LPS+rhNRG1+AG1478(ErbB4受体阻断剂)组,分别腹腔注射生理盐水、LPS 10mg/kg、LPS+rhNRG1 5mg/kg和LPS+rhNRG1+AG1478 20mg/kg。LPS给药后12h,检测各组大鼠心脏NRG1、磷酸化ErbB4(p-ErbB4)、ErbB4水平和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、左心室射血分数(LVEF)及左心室短轴缩短率(LVFS)。结果与对照组相比,LPS组大鼠心脏NRG1水平降低(P<0.05),LPS组及LPS+rhNRG1+AG1478组大鼠心脏p-ErbB4水平降低,LVEDD和LVESD增加,LVEF和LVFS降低(P<0.05)。与LPS组相比,LPS+rhNRG1组大鼠心脏NRG1、p-ErbB4水平增加,LVEDD和LVESD降低,LVEF和LVFS增加(P<0.05)。与LPS+rhNRG1组相比,LPS+rhNRG1+AG1478组大鼠心脏p-ErbB4水平降低,LVEDD和LVESD增加,LVEF和LVFS降低(P<0.05)。各组大鼠心脏ErbB4的表达均无统计学差异(P>0.05)。结论 NRG1-ErbB4信号通路功能下调与脓毒症大鼠心肌功能障碍密切相关。
Objective To investigate the role of neuregulin 1 （NRG1）-ErbB4 signal pathway in myocardial dysfunction in rats with sepsis. Methods Forty adult male SD rats were equally randomized into 4 groups of A（intraperitoneally injected normal saline as the control）, B[intraperitoneally injected lipopolysaccharide（LPS） 10 mg/kg], C （ intraperitoneally injected LPS plus rhNRG1 5 mg/kg） and D [intraperitoneally injected LPS plus rhNRG1 and AG1478 （an antagonist of ErbB4 receptors） 20 mg/kg]. At 12 hours after the administration of LPS, the expressions of NRG1, ErbB4 and p-ErbB4 in the hearts and the left ventricular end diastolic dimension（LVEDD）, left ventricular end systolic dimension（LVESD） ,left ventricular ejection fraction（LVEF） and left ventricular fractional shortening （LVFS） of rats were determined, respectively. Results Compared with group A, the NRG1 level in the hearts was decreased in group B（P〈0. 05）, the p-ErbB4 level in the hearts, LVEF and LVFS were decreased while LVEDD and LVESD were increased in groups of B and D（P〈0. 05）. Compared with group B, the levels of NRG1 and p-ErbB4 in the hearts, LVEF and LVFS were increased while LVEDD and LVESD were decreased in group C（P〈0. 05）. Compared with group C, the p-ErbB4 level in the hearts,LVEF and LVFS were decreased while LVEDD and LVESD were increased in group D （P〈0. 05）. There was no significant difference in the ErbB4 level of the hearts among four groups （P〉0. 05）. Conclusion The downregulation of the function of NRG1-ErbB4 signal pathway is closely related to myocardial dysfunction in rats with sepsis.
出处
《江苏医药》
CAS
2016年第3期262-265,共4页
Jiangsu Medical Journal
基金
江苏大学医学临床科技发展基金(JLY20120081)
金坛市科技计划项目(JT2013065)
