Akt 在 Ang-1、Ang-2调节失血性休克大鼠血管反应性双相变化中的作用

目的观察蛋白激酶B(PKB/Akt)在血管生成素-1(Ang-1)、血管生成素-2(Ang-2)调节失血性休克大鼠血管反应性双相变化中的作用。方法观察失血性休克后,以及Ang-1、Ang-2调节缺氧早期和晚期血管反应性过程中肠系膜上动脉(SMA)中Akt蛋白表达和磷酸化变化,并观察Akt抑制剂对Ang-1和Ang-2调节缺氧早期和晚期血管反应性作用的影响。结果 (1)失血性休克后SMA中Akt蛋白表达无明显改变,但磷酸化水平逐渐增高(P<0.01);(2)Akt抑制剂(1×10-5mol/L)可显著抑制缺氧10min的血管高反应性,也可显著抑制Ang-1对缺氧10min血管高反应性的维持作用(P<0.01);但对缺氧4h的血管低反应性和Ang-2降低缺氧4h血管反应性的作用无显著影响;(3)缺氧10min时,降低血管高反应性的Ang-2可降低Akt磷酸化;缺氧4h时,恢复血管低反应性的Ang-1和Tie-2抑制剂可抑制Akt磷酸化(P<0.01)。结论 Akt参与了休克早期Ang-1和Tie-2受体对血管高反应性的调节。

Role of Akt in the regulation of Ang-1 and Ang-2 on the biphasic change of vascular reactivity after hemorrhagic shock in rats

Objective To observe the role of Akt in the regulation of angiopoietin-1（Ang-1） and angiopoietin-2（Ang-2） on the biphasic change of vascular reactivity after hemorrhagic shock in rats.Methods The protein expression and phosphorylation of Akt in the superior mesenteric artery（SMA） after hemorrhagic shock,and during the regulation of Ang-1 and Ang-2 on vascular reactivity after hypoxia were measured,and the effect of Akt inhibitor on the vascular reactivity of SMA after hypoxia when treated with Ang-1 and Ang-2 were observed.Results（1） The protein expression of Akt in SMA was not significantly changed after hemorrhagic shock,yet the phosphorylation of Akt was increased significantly after hemorrhagic shock（P0.01）.（2） Akt inhibitor could decrease the vascular hyperreactivity at 10 minutes of hypoxia,and repress the maintenance effect of Ang-1 on vascular reactivity at 10 minutes of hypoxia,yet could not change the vascular reactivity at 4 hours of hypoxia or the effect of Ang-2 on the vascular reactivity at 4 hours of hypoxia group.（3） At 10 minutes of hypoxia,Ang-2 could decrease the phosphorylation of Akt（P0.01）;at 4 hours of hypoxia,Ang-1 and Tie-2 inhibitor could decrease the phosphorylation of Akt（P0.01）.Conclusion Akt contributes to the regulation of Ang-1 and Tie-2 on the vascular hyperreactivity in the early hemorrhagic shock.