摘要
目的探讨4-苯基丁酸(4-phenylbutyric acid,4-PBA)对脓毒症大鼠肺血管渗漏的作用及机制。方法采用盲肠结扎穿孔术(CLP)建立脓毒症大鼠模型,观察给予4-PBA后大鼠的肺血管通透性、内质网应激标志蛋白如葡萄糖调节蛋白78(glucose regulated protein78,GRP78)、葡萄糖调节蛋白94(glucose regulated protein94,GRP94)和CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer binding protein homologous protein,CHOP)表达的变化。培养大鼠肺静脉内皮细胞,观察给予脂多糖(Lipopolysaccharide,LPS)和4-PBA对细胞应力纤维(F-actin)的影响。结果与假手术组比较,脓毒症大鼠肺血管通透性显著升高,内质网应激标志蛋白(GRP78、GRP94、CHOP)的表达增高,4-PBA预处理后,脓毒症大鼠肺血管的通透性下降,内质网应激标志蛋白表达下降。与正常肺静脉内皮细胞比较,LPS组肺静脉内皮细胞应力纤维增多,细胞呈收缩状态。而4-PBA预处理组肺静脉内皮细胞形态则近似正常。结论 4-苯基丁酸可能通过抑制应力纤维形成,改善细胞收缩状态,降低脓毒症大鼠肺血管的通透性。
Objective To investigate the effect and mechanism of 4-phenylbutyric acid on pulmonary vascular permeability in sepsis rat. Methods With cecal ligation and puncture（ CLP） imitated sepsis model,the changes of pulmonary vascular permeability,endoplasmic reticulum stress marker proteins such as GRP78,GRP94 and CHOP of sepsis rat model were observed after applying 4-phenylbutyric. With culturing pulmonary vein endothelial cells,the influence of LPS or 4-PBA on F-actin was observed. Results As compared with the sham group,the pulmonary vascular permeability and the expression of endoplasmic reticulum stress marker proteins increased in the sepsis group.After perprocessing of 4-phenylbutyric acid,they decreased obviously. Conclusion 4-phenylbutyric acid can decrease the pulmonary vascular permeability of sepsis through inhibiting the formation of F-actin.
出处
《临床肺科杂志》
2015年第5期789-792,共4页
Journal of Clinical Pulmonary Medicine
关键词
4-苯基丁酸
脓毒症
血管渗漏
内质网应激
4-phenylbutyric acid
sepsis
vascular permeability
endoplasmic reticulum stress
