组蛋白去乙酰化酶抑制剂对50％总体表面积烫伤大鼠存活率和脏器功能的影响  

Effects of histone deacetylase inhibitor on survival and organ function of rats with 50% total body surface area fullthickness scald

作　　者：胡森[1] 白慧颖[1] 周国勇[1] 方涛[1] 刘先奇[1] 韩晓春[1] 盛志勇[1] 

机构地区：[1]解放军总医院第一附属医院烧伤研究所休克与多器官障碍实验室,北京100048

出　　处：《感染．炎症．修复》2010年第3期133-136,共4页Infection Inflammation Repair

基　　金：军队"十一五"科研基金专项课题(06Z055)

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂对无液体复苏时致死性烫伤休克大鼠存活率和脏器功能的改善作用。方法:64只SD雄性大鼠随机分为4组:假烫组(n=10),烫伤组(n=18),烫伤+2-甲基-2-乙酸组(2M2P组,n=18)和烫伤+丙戊酸钠组(VPANa组,n=18)。烫伤组于80℃水浴浸泡背部15 s、双下肢15 s、腹部8 s,造成50%TBSAⅢ度烫伤。假烫组于37℃水浴浸泡,部位和时间与烫伤组相同。2M2P组和VPANa组致伤方法同烫伤组,并于烫伤后即刻皮下注射2M2P或VPANa 300 mg/kg。各组大鼠烫伤深度经组织病理证实,于伤后2h和6 h取腹主动脉血检测血清丙氨酸转氨酶(ALT)、肌酐(Cr)和肌酸激酶同工酶(CK-MB)等脏器功能指标。另66只大鼠随机分为烫伤组(n=18)、2M2P组(n=24)和VPANa组(n=24),观察其伤后6 h和12 h生存率。结果:VPANa组生存时间为(776.7±89.5)min,显著高于烫伤组[(360.8±27.4)min]和2M2P组[(512.5±52.2)min],差异具有显著性(P<0.05)。VPANa组伤后6 h和12 h生存率分别为83.3%和50.0%,显著高于烫伤组(50.0%和0)和2M2P组(66.7%和16.7%),差异具有显著性(P<0.05);2M2P组6 h和12 h生存率也显著高于烫伤组(P<0.05)。烫伤及烫伤后各处理组伤后2 h和6 h ALT、Cr和CK-MB均显著高于假烫组(P<0.05)。伤后6h VPANa组ALT、Cr和CK-MB显著低于烫伤组和2M2P组(P均<0.05),2M2P组虽低于烫伤组,但差别无统计学意义。结论:组蛋白去乙酰化酶抑制剂能显著改善致死性烫伤休克大鼠脏器功能指标,延长动物生存时间。丙戊酸钠作用明显强于2M2P,有希望成为战场或灾害现场无液体复苏条件下救治致死性烧伤休克的潜力药物。Objective：To investigate the effect of histone deacetylase inhibitor in improving organ function and survival rate in rats with lethal burn shock without fluid resuscitation. Methods： Sixty-four male Sprague-Dawley rats were randomly divided into four groups： sham group（n= 10）, scald group （n= 18）, scald treated with 2- methyl-2-pentenoie acid group（2M2P group）, and scald treated with sodium valproate group （VPANa group）. Animals in scald group were exposed to a 80℃ water bath, 15 seconds for back, 15 seconds for both lower extremities, and 8 seconds for abdomen, resulting in full-thickness burn injury involving 50% TBSA. In sham group, 37℃ water bath was used for the same parts of the body with same time of exposure as those of the scald group. In 2M2P and VPANa group, 300 mg/kg 2M2P or VPANa were respectively injected hypodermically after scald injury. The depth of the burn was verified by pathological examination. All animals with scald injury were not given fluid resuscitation. The blood samples were collected at 2 hours and 6 hours after injury for the measurement of alanine aminotransferase（ALT） ,creatinine （Cr）, isoenzyme of creatine kinase（CK-MB）. In another group of 66 rats, the average survival time, and the survival rates at 6 hours and 12 hours of each group were recorded. Results：The average survival time of VPANa group was （776.7±89.5） minutes, which was significantly higher than that of scald group [（360. 8 ±27.4） minutes] and 2M2P group [（512.5 ±52. 2） minutes, P〈0. 05]. The survival rates at 6 hours and 12 hours in VPANa group were 83.3 ±and 50.0% respectively, which was significantly higher than those of scald group（50.0% and 0）and 2M2P group（66.7% and 16.7% ,all P〈0.05）. The 6- hour and 12-hour-survival rates of 2M2P group was higher than those of the scald group（P〈0.05）. The levels of ALT,Cr and CK-MB in all groups increased significantly after scald except the sham group. The levels of ALT,Cr and CK-MB of VPANa group

关 键 词：烧伤 休克 组蛋白去乙酰化酶抑制剂 药物治疗 丙戊酸钠 

分 类 号：R733.7[医药卫生—肿瘤]