组蛋白去乙酰酶抑制剂下调脓毒症小鼠肝内粘附分子表达  

Histone deacetylase inhibitors down-regulate hepatic expression of adhesion molecules in septic mice

作　　者：王彬[1] 张力[2] 万敬员[3] 姜蓉[2] 闵苏[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科 [2]重庆医科大学基础医学院病理生理学教研室 [3]重庆医科大学药学院药理学教研室,重庆400016

出　　处：《重庆医科大学学报》2011年第1期8-11,共4页Journal of Chongqing Medical University

基　　金：重庆市教委科学技术研究项目(编号:KJ090304)

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂对脓毒症小鼠肝内粘附分子表达及炎症细胞浸润的影响。方法:小鼠经腹腔注射组蛋白去乙酰化酶抑制剂(Trichostatin A或丁酸钠)后,行盲肠结扎穿孔术以诱导小鼠脓毒症。18 h后处死小鼠并收集血清和肝组织,检测血清转氨酶活性及肝组织匀浆髓过氧化物酶活性;常规石蜡切片HE染色观察组织病理学改变;免疫组织化学法检测肝组织内粘附分子(细胞间粘附分子-1及E-选择素)的表达水平。结果:2种结构不相关的组蛋白去乙酰化酶抑制剂均可下调脓毒症小鼠肝组织内粘附分子的表达,而肝组织HE染色切片上也观察到组蛋白去乙酰化酶抑制剂处理组肝内炎症细胞浸润明显减轻,与此一致,组蛋白去乙酰化酶抑制剂处理组肝组织匀浆中髓过氧化物酶活性及血清转氨酶活性显著降低。结论:组蛋白去乙酰化酶抑制剂处理组可下调脓毒症小鼠肝内粘附分子表达,从而减轻炎症细胞浸润和肝组织损伤。Objective：To investigate the effects of histone deacetylase（HDAC） inhibitors on the expression of adhesion molecules in liver tissue and the infiltration of leukocytes in liver tissue during the progression of sepsis.Methods：C57BL/6 mice were pre-treated with two structure unrelated HDAC inhibitors,Trichostatin A or sodium butyrate,and then sepsis was induced by cecal ligation and puncture（CLP）.At 18 h after CLP,hepatic expression of adhesion molecules,including intercellular adhesion molecule-1（ICAM-1） and E-selectin,were detected by immunohistochemical analysis.The formalin-fixed liver specimens were also stained with HE routinely for morphologic evaluation.In addition,myeloperoxidase（MPO） activity in liver tissue and serum aminotransferases levels were measured.Results：Treatment with HDC inhibitors down-regulated the expression of adhesion molecules.This was accompanied by reduced leukocyte infilatraion in the liver tissue,decreased MPO activity in hepatic homogenates as well as suppressed elevation of serum aminotransferases levels.Conclusion：HDAC inhibitors effectively suppressed the expression of adhesion molecules,thus significantly attenuated the recruitment of leukocytes and alleviated hepatic injury induced by sepsis.

关 键 词：组蛋白去乙酰化酶 脓毒症 粘附分子 炎症 盲肠结扎穿孔术 

分 类 号：R364.5[医药卫生—病理学]