CAJ | 학술논문

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。
목적：탐토조단백거을선화매억제제복립낙타(SAHA)대50%TBSAⅢ도탕상대서소장점막병장공능적보호작용。방법：웅성SD대서48지,체중240~260 g,수궤분위3조：①가탕조,우37℃수욕중배부침포15 s、복부침포8 s,행50%TBSA가탕후,립즉복강주사0.25 ml생리염수；②단탕조,100℃수욕탕상,상후립즉복강주사0.25 ml생리염수；③SAHA조,100℃수욕탕상후립즉복강주사0.25 ml SAHA주사액(7.5 mg/kg)。우상후3 h화6 h채용다보륵혈류의측정소장점막혈류량,취복주동맥혈검측혈청이알양화매(DAO)활성,면역형광쌍표법관찰장상피세포긴밀련접단백(ZO-1)적변화。결과：가탕조장점막혈류봉부,혈청중 DAO활성정상,장상피간 ZO-1형광신호강,정련속상태。여가탕조비교,단탕조상후장점막혈류량명현강저,상후3 h시강저58%,상후6 h시강저75%；DAO활성현저증고,상후3 h시증고248%,상후6 h시증고293%；장상피간ZO-1신호약,형광신호정현단렬상태。여단탕조비교,SAHA치료후탕상대서장점막혈류량현저증가,상후3 h시증가44%,상후6 h시증가45%；DAO활성명현강저,상후3 h시강저29%,상후6 h시강저34%；소장상피간ZO-1신호명현증강,ZO-1적단렬상태유소완해。결론：SAHA대엄중탕상대서인기적소장병장공능손해유명현적보호작용。
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.