丙戊酸钠对烧伤休克大鼠肺微血管内皮细胞活化和通透性的影响  

Effect of Sodium Valproate on Activation and Permeability of Pulmonary Microvascular Endothelium Cells in Rats with Burn Shock

作　　者：周国勇[1] 胡森[1] 贾赤宇[1] 

机构地区：[1]解放军309医院烧伤整形科,北京100091

出　　处：《解放军医药杂志》2013年第12期11-15,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金面上资助项目(81372051);国家重点基础研究发展计划(973计划)项目(2012CB518104);全军医学科技"十二五"重点课题(BWS11C061);北京市自然科学基金资助项目(7123229;7122179);中国博士后科学基金面上资助二等资助(2012M512081;2012M521846)

摘　　要：目的观察组蛋白去乙酰化酶抑制剂丙戊酸钠(VPA)对大鼠50%TBSAⅢ度烧伤休克模型肺微血管内皮细胞(PMEC)活化和通透性的影响。方法雄性SD大鼠随机分为4组:假烫组,烫伤组(给予50%TBSAⅢ度烫伤),烫伤+VPA组及烫伤+2M2P组(烫伤后即刻皮下注射VPA 300 mg/kg或对照药物2-甲基-2-戊烯酸,即2M2P300 mg/kg)。分别于烫伤后2 h、6 h及12 h,伊文斯蓝(EB)染色法检测肺血管通透性;采血检测红细胞压积(HCT)及脏器功能指标;HE染色观察肺组织病理变化,干湿重法检测肺组织含水率;免疫组化法检测肺组织血管内皮细胞生长因子(VEGF)、E-选择素(E-selectin)和细胞间黏附分子-1(ICAM-1)的表达;TUNEL法检测肺微血管内皮细胞(PMEC)凋亡率。结果与烫伤组比较,伤后2 h及6 h烫伤+VPA组和烫伤+2M2P组血HCT和肺组织含水率降低,肺血管通透性明显降低(P<0.05),肺水肿等病理改变减轻;烫伤+VPA组PMEC凋亡率低于烫伤+2M2P组(P<0.05)。烫伤+VPA组VEGF、E-selectin、ICAM-1阳性率均显著低于烫伤组和烫伤+2M2P组(P<0.05)。结论 VPA能抑制烧伤休克大鼠肺血管内皮细胞的活化以及凋亡,从而减少血管通透性增加引起的血容量丢失。Objective To observe the effect of Sodium Valproate（ VPA） on activation and permeability of pulmonary microvascular endothelium cells（ PMEC） in burn shock rats with third degree burn and 50% TBSA. Methods Male SD rats were randomly divided into sham group（ group A）,ambustion group suffered 50% TBSA ambustion（ group B）,ambustion and VPA group（ group C） and ambustion and 2-methyl-2-pentenoic acid group（ 2M2P,group D）,and the group D was subcutaneously injected with 300 mg /kg VPA or 300 mg /kg 2M2P after injury. Pulmonary vascular permeabilities were detected with evans blue（ EB） staining method at 2,6 and 12 h postinjury; haematocrit（ HCT） and organ function indexes were detected by blood collection; pathological changes and water content of lung tissues were observed with hematoxylin and eosin（ HE） stain method and detected with oven drying method respectively; meanwhile expressions of vascular endothelial cell growth factor（ VEGF）,E-selectin and ICAM-1 contents were detected with immunohistochemical method; apoptosis rates of pulmonary microvascular endothelial cell（ PMECs） were detected with TUNEL method. Results Compared with group B,blood HCT levels,water contents and permeability of pulmonary tissues at 2 h and 6 h postinjury were significantly lower in group C and D（ P ＆lt; 0. 05）,and pathological changes in the two groups were also alleviated; while the apoptosis rate of PMECs in group C was significantly lower than that in group D（ P ＆lt;0. 05）. Expressions of VEGF,E-selectin and ICAM-1 positive rates in group C were significantly lower than those in group B and D（ P ＆lt; 0. 05）. Conclusion VPA can inhibit activation and apoptosis of PMECs in rats with burn shocks,which may decrease blood volume losses induced by the increase of vascular permeability.

关 键 词：烧伤 休克 丙戊酸 肺微血管内皮细胞 大鼠 Sprague-Dawley 

分 类 号：R-332[医药卫生]