伏立诺他对烫伤大鼠小肠屏障功能保护作用的研究  

Protective effects of suberoylanilide hydroxamic acid on scald-induced gut barrier dysfunction in rats

作　　者：童斌[1] 白晓东[2] 王婧婧[2] 赵增凯[1] 罗红敏[1] 张慧萍[1] 吕艺[1] 孟祥熙[1] 胡森[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 [2]武警总医院烧伤整形科,北京100039

出　　处：《感染．炎症．修复》2014年第1期23-26,F0003,共5页Infection Inflammation Repair

基　　金：军队"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伏立诺他（SAHA）对50%TBSAⅢ度烫伤大鼠小肠黏膜屏障功能的保护作用。方法：雄性SD大鼠48只,体重240~260 g,随机分为3组：①假烫组,于37℃水浴中背部浸泡15 s、腹部浸泡8 s,行50%TBSA假烫后,立即腹腔注射0.25 ml生理盐水；②单烫组,100℃水浴烫伤,伤后立即腹腔注射0.25 ml生理盐水；③SAHA组,100℃水浴烫伤后立即腹腔注射0.25 ml SAHA注射液（7.5 mg/kg）。于伤后3 h和6 h采用多普勒血流仪测定小肠黏膜血流量,取腹主动脉血检测血清二胺氧化酶（DAO）活性,免疫荧光双标法观察肠上皮细胞紧密连接蛋白（ZO-1）的变化。结果：假烫组肠黏膜血流丰富,血清中 DAO活性正常,肠上皮间 ZO-1荧光信号强,呈连续状态。与假烫组比较,单烫组伤后肠黏膜血流量明显降低,伤后3 h时降低58%,伤后6 h时降低75%；DAO活性显著增高,伤后3 h时增高248%,伤后6 h时增高293%；肠上皮间ZO-1信号弱,荧光信号呈现断裂状态。与单烫组比较,SAHA治疗后烫伤大鼠肠黏膜血流量显著增加,伤后3 h时增加44%,伤后6 h时增加45%；DAO活性明显降低,伤后3 h时降低29%,伤后6 h时降低34%；小肠上皮间ZO-1信号明显增强,ZO-1的断裂状态有所缓解。结论：SAHA对严重烫伤大鼠引起的小肠屏障功能损害有明显的保护作用。Objective：To investigate the protective effect of histone deacetylase inhibitor,suberoylanilide hydroxamic acid （SAHA）,on gut barrier dysfunction in rats with 50%TBSA full-thickness burns.Methods：Forty-eight male SD rats,weig-hing 240-260 g,were randomly divided into three groups：sham control group,scald group and SAHA group. Full thickness scald injury involving 50% TBSA was replicated by immersing the back and abdomen in 100 ℃ water for 15 and 8 seconds respectively in rats of scald group and SAHA group,and then 0.25 ml normal saline or 0.25 ml （7.5 mg/kg）SAHA was intraperitoneally injected,respectively. In the sham control group,37 ℃ water was used instead of 100 ℃ water,and 0.25 ml normal saline was intraperitoneally inj ected after sham inj ury. Blood flow （IMBF）of small intestine was measured by Doppler 3 and 6 hours after scald inj ury,while the activity of serum diamine oxidase （DAO）was determined,the expression of intestinal epithelial tight junction protein （ZO-1）of terminal ileum tissue was determined with immunofluorescence. Re-sults：In sham control group,IMBF was rich,the activity of DAO in serum was normal,the expression of intestinal epithelial ZO-1 was strong,presenting in a continuous state. Compared to sham control group,IMBF in scald group was significantly reduced by 58% at 3 hours and 75% at 6 hours after scald injury. The activity of DAO increased by 248% at 3 hours and 293% at 6 hours after scald injury. The expression of intestinal epithelial ZO-1 was weaker,and the fluorescence signal showed broken state. Compared to the scald group,IMBF in SAHA treatment group significantly increased by 44% at 3 hours and 45% at 6 hours after injury,and the activity of DAO was significantly decreased by 29%at 3 hours and 34%at 6 hours after inj ury,while the signal of intestinal epithelial ZO-1 was marked enhanced. Conclusions：SAHA has a significant protective effect on intestinal barrier function in rats suffering from severe burn inj ury.

关 键 词：伏立诺他 烫伤 肠屏障 上皮间紧密连接蛋白 

分 类 号：R285.5[医药卫生—中药学]