Ulinastatin mediates protection against vascular hyperpermeability following hemorrhagic shock

摘要: Object: Recent studies have suggested that intrinsic apoptotic signaling cascade is involved in endothelial barrier dysfunction following hemorrhagic shock (HS), which results vascular hyperpermeability. Our previous study demonstrated ulinastatin (UTI) inhibits oxidant-induced hyperpermeability and signaling. In present study, we hypothesized UTI would improve HS-induced by regulating the cascade. Methods: Hemorrhagic was induced rats withdrawing blood to reduce mean arterial pressure 40-45 mmHg for 60 min, followed reperfusion. Mesenteric postcapillary venules were examined changes intravital microscopy. vitro, Rat lung microvascular cells (RLMVECs) exposed serum 120 transendothelial electrical resistance (TER) estimation. Mitochondrial release of cytochrome c caspase-3 activation estimated vivo. ratio cell apoptosis evaluated Annexin-V/PI double stain assay; mitochondrial membrane potential (∆Ψm) determined with JC-1; intracellular ATP content assayed a commercial kit; reactive oxygen species (ROS) measured DCFH-DA; adherens junction protein β-catenin detected immunofluorescense staining. Results: vivo, attenuated versus HS group (P < 0.05); RLMEC monolayer 0.05). inhibited apoptosis, low level, ∆Ψm depolarization, ROS increase improved pre-treatment disruption junction. Conclusions: HS. regulates oxidative stress