胍丁胺对脓毒症小鼠血管内皮损伤的保护作用  

The protective effect of agmatine on vascular endothelial dysfunction in septic mice

作　　者：杨霞[1] 朱俊宇[2] 范霞[2] 杨雪[2] 唐婉琦 马娓 梁华平[2] 马松涛[1] 

机构地区：[1]成都医学院,四川成都610500 [2]第三军医大学大坪医院野战外科研究所一室,创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中国中西医结合急救杂志》2016年第2期182-185,共4页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：创伤、烧伤与复合伤国家重点实验室项目（BWS11J038）;国家重点基础研究发展计划项目（2012CB518102）

摘　　要：目的探讨胍丁胺对脓毒症小鼠血管内皮功能的影响。方法将42只C57BL／6小鼠按随机数字表法分为假手术组、模型组、胍丁胺治疗组，每组14只。采用盲肠结扎穿孔术（CLP）复制脓毒症小鼠模型；假手术组只开腹不进行结扎穿孔术，术后腹腔注射磷酸盐缓冲液。胍丁胺组术后腹腔注射400mg／kg胍丁胺；其余两组术后腹腔注射等量磷酸盐缓冲液。于制模后24h处死小鼠取血，采用酶联免疫吸附试验（ELISA）检测血清细胞间黏附分子-1（ICAM-1）、血管间黏附分子-1（VCAM-1）、血管内皮生长因子（VEGF）、血管性血友病因子（vWF）、血管紧张素-Ⅱ（Ang-Ⅱ）、单核细胞趋化因子-1（MCP-1）、肿瘤坏死因子-α．（TNF-α）、白细胞介素（IL-6、IL-10）的含量；通过异硫氰酸荧光素（FITC）-葡聚糖荧光示踪法检测肝、肺组织的血管通透性。结果造模后24h，模型组小鼠腹部呈浅粉色、体温下降、精神萎靡、活动减少；胍丁胺组小鼠治疗后精神和活动状态均有明显好转。与假手术组比较，模型组血管内皮相关生物标志物的含量均显著升高[ICAM-1（ng／L）：9887．12±897．90比4747．12±958．00，VCAM-1（ng／L）：2884．09±230．00比1349．43±238．47，vWF（ng／L）：48．61±0．69比31．82±2．38，VEGF（ng／L）：45．14±1．76比20．65±0．57，Ang-1I（ng／L）：13．26±0．84比8．87±0．80，MCP-1（ngJL）：1881．3l±106．71比66．21±6．68，均P〈0．01]；胍丁胺组上述各指标含量均较模型组明显降低[ICAM-1（ng／L）：6380．45±1017．73比9887．12±897．90，VCAM-1（ng／L）：1894．76±235．39比2884．09±230．00，vWF（ng／L）：37．77±4．42比48．61±0．69，VEGF（ng／L）：32．19±1．96比45．14±1．76．Ang-Ⅱ（ng／Ⅱ）：10．81±0．45比13．26±0．84，MCP-1（ng／L）：553．58±56．19比188131±106．71，均P〈0．01j。l司时，与假手术比较�Objective To explore the efficiency of agmatine on vascular endothelial dysfunction in septic mice. Methods Forty-two C57BL/6 mice were randomly divided into three groups： sham operation group, model group, agmatine treatment group （n = 14 in each group）. The cecal ligation and puncture （CLP） was conducted to establish sepsis model; the sham operation group received laparotomy only without cecal ligation and puneture. In agmatine treatment group, 400 mg/kg agmatine dissolved in phosphate buffer saline was injected intraperitoneally after operation; in other two groups, postoperatively the same amount of phosphate buffer saline was intraperitoneally injected. Twenty-four hours after model establishment, the mice were sacrificed, and blood samples were collected for detecting the contents of serum soluble intercellular adhesion molecule-1 （ICAM-1）, soluble vascular cell adhesion molecule-1 （VCAM-1）, vascular endothelial growth factor （VEGF）, yon Willebrand factor （vWF）, angiopoietin-Ⅱ （Ang-Ⅱ） and monoeyte chemotactie protein-1 （MCP-1）, tumor necrosis faetor-α （TNF-α）, interleukin （IL-6 and IL-10） by enzyme linked immunosorbent assay （ELISA）. The fluorescein trace method of isothiocyanate （FITC）-dextran was used to measure the pulmonary and hepatic vascular permeability in vivo. Results Twenty-four hours after modeling, the abdomen of mice showed light pink in color, the body temperature was lowered, the spirit was drooping and the activity was less in model group; while in agmatine treatment group, the spirit and activity status of mice wassignificantly better. Compared with sham operation group, the levels of vascular endothelium related biomarkers in model group were significantly elevated [ICAM-1 （ng/L）： 9887.12 ± 897.90 vs. 4747.12 ± 958.00; VCAM-1 （ng/L）： 2884.09 ± 230.00 vs. 1 349.43 ± 238.47; vWF （ng/L）： 48.61 ±0.69 vs. 31.82± 2.38; VEGF （ng/L）： 45.14± 1.76 vs. 20.65 ± 0.57; Ang-U （ng/L）： 13.26 ± 0.84 vs. 8.87 ± 0

关 键 词：胍丁胺 脓毒症 盲肠结扎穿孔术 血管内皮 

分 类 号：R378.2[医药卫生—病原生物学]