神经调节蛋白-1对脓毒症大鼠心肌组织炎症和心肌细胞凋亡的影响

Effects of neuregulin-1 on myocardial inflammation and cardiomyocyte apoptosis in rats with sepsis

目的研究神经调节蛋白-1(neuregulin-1,NRG-1)对脓毒症大鼠心肌组织炎症和心肌细胞凋亡的影响。方法雄性(8-10周)SD大鼠随机分为脓毒症组(n=10)、脓毒症NRG组(n=10)、假手术组(n=5)及假手术NRG组(n=5)。脓毒症组和脓毒症NRG组建立盲肠结扎穿孔模型(cecal ligation puncture,CLP),假手术NRG组和脓毒症NRG组手术前30 min尾静脉注射重组人神经蛋白1(rhNRG-1,0.01μg/g),而假手术组和脓毒症组均于手术前30 min尾静脉注射等量生理盐水。术后24 h检测大鼠血流动力学,Western blot检测大鼠左心室组织的炎症因子TNF-α、IL-1β及IL-6,TUNEL法检测右心室组织细胞凋亡。结果与假手术组相比,脓毒症组平均动脉压(MAP)、左心室收缩压(LVSP)和左室内压最大发展速率(±d P/dt max)降低(P<0.05),左心室舒张末压(LVEDP)升高(P<0.05),心肌炎症因子增加(P<0.05),凋亡细胞增多(P<0.05);与脓毒症组比较,脓毒症NRG组MAP、LVSP、±d P/dtmax增加(P<0.05),LVEDP降低(P<0.05),心肌炎症因子降低(P<0.05),凋亡细胞减少(P<0.05)。结论神经调节蛋白-1可以改善脓毒症大鼠血流动力学、减轻心肌组织炎症,减少心肌细胞凋亡。

Objective To explore the effect of neuregulin-1（ NRG-1） on myocardial inflammation and cardiomyocyte apoptosis in rats with sepsis. Methods Male（ 8-10 weeks old） SD rats were randomly divided into sepsis group（ n = 10）,sepsis NRG group（ n =10）,sham group（ n = 5） and sham NRG group（ n = 5）. The cecal ligation puncture（ CLP） sepsis model was established in sepsis group and sepsis NRG group. The rats were injected with rh NRG at the dose of 0. 01 μg/g through tail vein 30 min before surgery in sham NRG group and sepsis NRG group,and the rats were given the same amount of saline via tail vein 30 min before surgery in sham group and sepsis group. The hemodynamics of the rats was measured at 24 h after operation. Western blot was used to detect the expression of TNF-α,IL-1β and IL-6 in the left ventricle of rats,and the apoptosis of right ventricular tissue was detected by TUNEL.Results Compared with sham group,the mean arterial pressure（ MAP）,the left ventricular systolic pressure（ LVSP） and ± d P/dtmax of the rats were decreased in sepsis group（ P〈0. 05）,while the left ventricular end diastolic,myocardial inflammatory factors and the apoptotic cells of the rats were increased（ P〈0. 05）. Compared with sepsis group,the mean arterial pressure（ MAP）,the left ventricular systolic pressure（ LVSP） and ± d P/dtmax of the rats were increased in sepsis NRG group（ P〈0. 05）,while the left ventricular end diastolic pressure（ LVEDP）,the level of myocardial inflammatory factors,and the apoptotic cells of the rats were decreased（ P〈0. 05）. Conclusion Neuregulin-1 can improve the hemodynamics of sepsis rats,reduce the inflammation of myocardium and reduce myocardial cell apoptosis.