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首页> 外文期刊>American Journal of Physiology >Angiopoietin-1 inhibits intrinsic apoptotic signaling and vascular hyperpermeability following hemorrhagic shock
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Angiopoietin-1 inhibits intrinsic apoptotic signaling and vascular hyperpermeability following hemorrhagic shock

机译：血管生成素-1抑制失血性休克后固有的凋亡信号和血管通透性高

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Studies from our laboratory demonstrated the involvement of intrinsic apoptotic signaling in hyperpenneability following hemorrhagic shock (HS). Angiopoietin 1 (Ang-1), a potent inhibitor of hyperpenneability, was recently shown to inhibit apoptosis. The purpose of our study was to determine the effectiveness of Ang-1 in attenuating HS-induced hyperpermeability and its relationship to apoptotic signaling. HS was induced in rats by withdrawing blood to reduce the mean arterial pressure to 40 mmHg for 1 h, followed by reperfusion. Mesenteric postcapillary venules were examined for changes in hyperpermeability by intravital microscopy. Mitochondrial release of second mitochondrialderived activator of caspases (smac) and cytochrome c were determined by Western blot and ELISA, respectively. Caspase-3 activity was determined by ftuorometric assay. Parallel studies were performed in rat lung microvascular endothelial cell (RLMEC) mono-layers, utilizing HS serum and the proapoptotic Bcl-2 homologous antagonist/killer [BAK (BH3)] peptide as inducers of hyperpermeability. In rats, Ang-1 (200 ng/ml) attenuated HS-induced hyperpermeability versus the HS group (P < 0.05). Ang-1 prevented HS-induced collapse of mitochondrial transmembrane potential (DELTA PSI_m), smac and cytochrome c release, and caspase-3 activity (P < 0.05). In RLMEC monolayers, HS serum and BAK (BH3) peptide both induced hyperpermeability that was inhibited by Ang-1 (P < 0.05). Ang-1 attenuated HS and BAK (BH3) peptide-induced collapse of DELTA PSI_m, smac release, cytochrome c release, activation of caspase-3, and vascular hyperpermeability. In vivo, BAK (BH3) induced vascular hyperpermeability that was attenuated by Ang-1 (P < 0.05). These findings suggest that Ang-1's role in maintaining microvascular endothelial barrier integrity involves the intrinsic apoptotic signaling cascade.
机译：我们实验室的研究表明出血性休克（HS）后内在的凋亡信号参与了高通透性。血管生成素1（Ang-1），一种高通透性抑制剂，最近被证实可以抑制细胞凋亡。我们研究的目的是确定Ang-1在减弱HS诱导的通透性及其与凋亡信号传导之间的关系。通过抽血将平均动脉压降至40 mmHg 1小时，然后再灌注，在大鼠中诱导HS。通过活体显微镜检查肠系膜后毛细血管的通透性变化。半胱天冬酶（smac）和细胞色素c的第二个线粒体衍生激活剂的线粒体释放分别通过Western印迹和ELISA确定。通过荧光测定法测定Caspase-3活性。在大鼠肺微血管内皮细胞（RLMEC）单层中进行平行研究，利用HS血清和促凋亡Bcl-2同源拮抗剂/杀伤剂[BAK（BH3）]肽作为高通透性诱导剂。在大鼠中，Ang-1（200 ng / ml）与HS组相比减弱了HS诱导的通透性（P <0.05）。 Ang-1阻止了HS诱导的线粒体跨膜电位（DELTA PSI_m）崩溃，smac和细胞色素c释放以及caspase-3活性（P <0.05）。在RLMEC单层中，HS血清和BAK（BH3）肽均可诱导被Ang-1抑制的高通透性（P <0.05）。 Ang-1减弱了HS和BAK（BH3）肽引起的DELTA PSI_m崩溃，smac释放，细胞色素c释放，caspase-3活化和血管通透性过高。在体内，BAK（BH3）诱导的血管通透性被Ang-1减弱（P <0.05）。这些发现表明，Ang-1在维持微血管内皮屏障完整性中的作用涉及内在的凋亡信号级联。

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