过氧化物酶体增殖物激活受体-γ激动剂对脓毒症大鼠内皮损伤的作用  

Effects of proliferator-activated receptor-γ agonist on vascular endothelial injuries in septic rats

作　　者：王静[1] 戴琳 于鲁欣[1] 孙艺铸[1] 

机构地区：[1]烟台毓璜顶医院重症医学科,山东省264000 [2]烟台山医院心电图室

出　　处：《中华医学杂志》2015年第15期1179-1183,共5页National Medical Journal of China

基　　金：山东省自然科技基金（C2008K151）

摘　　要：目的 探讨过氧化物酶体增殖物激活受体-γ（PPAR-γ）人工合成配体罗格列酮（ROSI）对脂多糖（LPS）诱导的脓毒症大鼠内皮损伤的作用.方法 健康雄性SD大鼠40只,随机分为4组（每组10只）：正常对照组;LPS刺激组;罗格列酮（ROSI）预处理组;选择性拮抗剂2-氯-5-硝基苯胺（GW9662）预处理组.在每组操作结束后4h取血.免疫细胞化学结合图像分析法检测外周血单个核细胞（PBMC）内PPAR-γ的表达活性.内皮损伤标志物包括血管细胞黏附分子（VCAM-1）、细胞间黏附分子（ICAM-1）、血管生成素-2（Ang-2）、血栓调节蛋白（TM）、抗凝血酶-Ⅲ（AT-Ⅲ）、组织因子（TF）、vWF因子（vWF）和循环内皮细胞（CEC）.结果 ROSI组PPAR-γ表达与LPS刺激组比较显著增加（111.0 ±4.1,P＜1.01）.GW9662组PPAR-γ表达显著降低,与正常组比较差异无统计学意义（44.2 ±264.0,P＞1.05）.VEC诱导的VCAM-1、ICAM-1、Ang-2、TM、AT-Ⅲ、TF、vWF在LPS组明显升高,与正常对照组比较差异有统计学意义（P＜0.01）.ROSI预处理则大大减轻了这些指标的升高,与LPS组比较差异有统计学意义（P＜0.01）.GW9662预处理组与LPS组比较差异无统计学意义（P＞0.05）.反映VEC凋亡的标志物外周血CEC数量在LPS组明显升高,与正常对照组比较差异有统计学意义（P＜0.01）.ROSI预处理则大大减轻了CEC数量的升高,与LPS组比较差异有统计学意义（P＜0.01）.GW9662预处理组与LPS组比较差异无统计学意义[（5.2±0.8）个/μl比（5.7±0.6）个/μl,P＞1.05].结论 过氧化物酶体增殖物激活受体-γ激动剂能够改善脓毒症导致的内皮损伤,其机制可能与其稳定血管内皮细胞,改善严重炎症反应和凝血功能紊乱有关.Objective To explore the effects of rosiglitazone,a synthetic Iigand of proliferator-activated receptor-γ （PPAR-γ） on vascular endothelial injuries in septic rats.Methods A total of 40 male Sprague-Dawley rats were randomly divided into 4 groups of vehicle control,lipopolysaccharide （LPS）,pretreatment of rosiglitazone （ROSI） and pretreatment of PPAR-γ antagonist 2-chloro-5-nitroaniline （GW9662） （n =10 each）.At 4 hours post-intervention,blood samples were collected to detect the expression of PPAR-γby immunocytochemistry and image analysis.And the following parameters of vascular endothelial injury were measured：Vascular cell adhesion molecule-1 （VCAM-1）,intercellular adhesion molecule-1 （ICAM-1）,angiopoietin-2 （Ang-2）,thrombomodulin （TM）,anti-thrombin Ⅲ （AT-Ⅲ）,tissue factor （TF）,von Willebrand factor （vWF） and circulating endothelial cell （CEC）.Results ① In ROSI group,the expression of PPAR-γ was significantly higher than that in LPS group （P 〈 0.01）.In GW9662 group,the expression of PPAR-γ had no significant difference compared to vehicle control group （P 〉0.05）.② The serum concentrations of VCAM-1,ICAM-1,Ang-2,TM,AT-Ⅲ,TF and vWF were significantly higher in LPS group than those in vehicle control group （P 〈 0.01）.The concentrations of these parameters in ROSI group were significantly lower than those in LPS group （P 〈 1.01）.In GW9662 group,the concentrations of these parameters had no significant difference compared with LPS group （P 〉 0.05）.③The numbers of CEC were significantly higher in LPS group than those in vehicle control group （P 〈 0.01）.And the numbers of CEC were significantly lower in ROSI group than those in LPS group （P 〈 0.01）.In GW9662 group,the numbers of CEC had no significant difference compared with LPS group （P 〉 0.05）.Conclusion Proliferator-activated receptor-γ agonist improves sepsis-induced vascular endothelial injury.And its mechanism may be through stabilizing vascul

关 键 词：脓毒症 过氧化物酶体类 内皮 血管 增殖物激活受体-γ 

分 类 号：R459.7[医药卫生—急诊医学]