组蛋白去乙酰化酶抑制剂对50%TBSAⅢ度烫伤休克大鼠生存率及微血管通透性影响  

Protective effects of histone deacetylase inhibitor on survival and permeability of pulmonary microvascular endothelium in 50% TBSA full-thickness burn in rat model

作　　者：方涛[1] 胡森[2] 白慧颖[2] 周国勇[2] 盛志勇[2] 

机构地区：[1]天津市第四中心医院,300140 [2]解放军总医院第一附属医院全军烧伤研究所,北京100037

出　　处：《武警医学》2013年第7期564-567,571,共5页Medical Journal of the Chinese People's Armed Police Force

基　　金：全军医学科研"十一五"专项课题(06Z055)

摘　　要：目的探讨组蛋白去乙酰化酶抑制剂(HDACI)在无液体复苏条件下对50%TBSAⅢ度烫伤休克大鼠生存率及各重要脏器血管通透性的影响。方法雄性SD大鼠,前期麻醉后行颈、躯干及双下肢备皮,行水浴造成全身50%TBSAⅢ度烫伤,约(50.4±3.8)%体表面积。78只雄性SD大鼠,随机分为①假烫组、②烫伤组、③烫伤+2M2P组、④烫伤+VPA组。烫伤后③、④组分别皮下注射2-甲基-2-乙酸(2M2P 300 mg/kg)、丙戊酸钠(VPA 300 mg/kg),观察各组生存时间。另160只大鼠分组处理同前,于烫伤后6 h,采用伊文斯蓝(EB)染色法检测各重要脏器(心脏、肝脏、肾脏、小肠)血管通透性;干湿重法检测各脏器组织含水率;腹主动脉取血检测各组肿瘤坏死因子-α(TNF-α)和2,3-二磷酸甘油酸(2,3-DPG)水平。结果烫伤后VPA组12 h生存率为50%,可明显延长烫伤休克大鼠生存时间,VPA组大鼠生存时间为(13.56±1.27)h,显著高于烫伤组中[(6.21±0.45)h]及2M2P组[(8.51±0.73)h]。烫伤后6 h VPA组大鼠心脏、肝脏、肾脏、小肠组织含水率及组织通透性均低于2M2P组及假烫组(P<0.05)。血浆TNF-α水平VPA组均显著低于烫伤组和2M2P组(P<0.05);而2,3-DPG含量VPA组则高于烫伤组和2M2P组(P<0.05)。结论组蛋白去乙酰化酶抑制剂可降低脏器血管通透性,减少液体丢失,提高烫伤休克大鼠生存率,其作用机制可能与降低TNF-α的含量抑制其炎性反应发生,提高2,3-二磷酸甘油酸水平提升红细胞供氧能力有关。Objective To test whether administration of HDACI （VPA and 2M2P）, without fluid resuscitation, can improve permeability of microvascular endothelium and survival rate in shock rats with 50% TBSA full - thickness burn injury. Methods Rats were subjected to 50% TBSA full - thickness burn injury. The back, legs, abdominal and right cervical area of male Sprague - Dawley （SD） rats were shaved under anesthesia. After that, the rats were subjected to a 50% （50.4% ± 3.8% ）total body surface area（ TBSA） fullthickness flame injury under anesthesia. Seventy- eight male rats were randomized divided into：① no burn shock （sham） group, ② burn shock with no resuscitation （NR） group, ③ burn shock with valproic acid （VPA） group, and ④ burn shock with 2 - methyl -2 - pentenoic acid （2M2P） group. Both VPA and 2M2P groups were injected immediately after bum shock at 300 mg/kg sep- arately. After that, both the average survival time and survival rates were recorded. In another group of 160 rats, survival rats at 6 hour were examined for vascular permeability of organs with Evans blue staining method. Tissues of heart, liver, kidneys and jejunum were harvested for determination of water contents by oven drying method. After this process, blood samples were taken from ventral aorta at baseline, for the measurement of levels of TNF -α and 2,3 - DPG in plasma. Results VPA enhanced the duration of survival. After burn shock, 50% （VPA） pretreated rats were alive versus 0% in NR group at 12 hours. In both VPA and 2M2P groups, the survival of severely burn shock rats increased, the pro - survival effects of VPA administration were dramatic. The average survival time in VPA group was 13.56 h significantly longer than those in 2M2P group （ 8.51 h） and scalded group （ 6.21 h） （ P 〈 0.05 ）. The water contents and organ vascular pearmeability in the three groups of rats were increased, lower in VPA group than in 2M2P group and NR group. The levels of TNF -α and 2,3 - DPG in plasma of

关 键 词：烫伤 休克 组蛋白去乙酰化酶抑制剂 血管通透性 

分 类 号：R644[医药卫生—外科学]