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目的研究脓毒性休克大鼠内质网应激模型中葡萄糖调节蛋白78(glucose-regulated protein78,GRP78)和C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(C/EBP homologous protein,CHOP)蛋白表达的变化及其与血管通透性改变的关系。方法 42只成年SD大鼠,雌雄各半,体质量200~220 g,随机分为3组:①假手术组;②盲肠造瘘组,按照术后时间长短盲肠造瘘组又分为术后1、2、4、6、8 h等5个亚组;③盲肠造瘘+牛磺酸组(n=6)。用异硫氰酸荧光素标记的牛血清白蛋白注入肺组织,在术后1、2、4、6、8 h时分别取各组相应大鼠肺脏,牛磺酸干预组于术后6 h取出,生理盐水进行肺灌洗,观察其荧光物质渗透率的变化测量肺毛细血管通透性;Western blot方法测量肺血管内皮细胞GRP78和CHOP蛋白的表达并对各组进行比较。结果①大鼠盲肠造瘘术后1、2、4、6、8 h后GRP78和CHOP蛋白表达均呈递增趋势[(P(GRP78)<0.05;P(CHOP)<0.05],肺血管荧光物质渗透率也随着时间的延长呈直线递增的趋势(P=0.006<0.05),盲肠造瘘组各组GRP78和CHOP蛋白的表达与肺血管荧光物质渗透率的改变呈正相关(R2=0.785,P<0.05;R2=0.881,P<0.05);②牛磺酸处理后,6 h点肺血管荧光物质渗透率显著低于单纯盲肠造瘘术后(P=0.007<0.05),GRP78和CHOP蛋白的表达也较盲肠造瘘组低(P=0.004<0.05)。结论脓毒性休克内质网应激参与了血管通透性增高的发生,GRP78和CHOP蛋白为重要的参与分子。
Objective To investigate the effects of glucose-regulated protein78 (GRP78) and cyclic C / EBP cyclic adenosine monophosphate (CEPP) homologous protein (CHOP) on endoplasmic reticulum stress in septic shock rats. ) Protein expression and its relationship with vascular permeability changes. Methods 42 adult SD rats, male and female, weighing 200-220 g, were randomly divided into three groups: ① sham operation group; ② cecal ostomy group, according to the length of postoperative cecal fistula group was divided into postoperative 1,2,4,6,8 h and other 5 subgroups; ③ cecal fistula + taurine group (n = 6). Fluorescein isothiocyanate labeled bovine serum albumin into the lung tissue at 1, 2, 4, 6, 8 h after the respective groups were taken from each rat lung, taurine intervention group after 6 h Removed, saline lavage, changes in the permeability of the fluorophores were observed to measure pulmonary capillary permeability; Western blot was used to measure the expression of GRP78 and CHOP protein in the vascular endothelial cells and the comparison of each group. Results ① After 1, 2, 4, 6, 8 h, the expressions of GRP78 and CHOP protein in the rats were both increased (P (GRP78) <0.05; P (CHOP) <0.05] The permeability also increased linearly with time (P = 0.006 <0.05). The expression of GRP78 and CHOP protein in each group of cecal fistula was positively correlated with the change of pulmonary vascular permeability (R2 = 0.785, P (P <0.05; R2 = 0.881, P <0.05). ② The permeability of pulmonary vascular endothelial cells at 6 h after taurine treatment was significantly lower than that after simple cecostomy (P = 0.007 <0.05) (P = 0.004 <0.05) .Conclusion Endoplasmic reticulum stress in septic shock is involved in the increase of vascular permeability, GRP78 and CHOP proteins are important involved molecules.