6甲酰基吲哚并[3,2-b]咔唑对脂多糖诱导的急性呼吸窘迫综合征大鼠的保护作用  

Protective effects of 6-formylindolo [3,2-b]carbazole against LPS-induced acute respiratory distress syndrome in rats

作　　者：魏佳鑫[1] 范霞[2] 张莹[2] 陈浩[2] 黄文娟[1] 梁华平[1,2] 

机构地区：[1]遵义医学院附属医院重症医学科,贵州遵义563003 [2]第三军医大学大坪医院野战外科研究所第一研究室、创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《第三军医大学学报》2016年第22期2419-2423,共5页Journal of Third Military Medical University

基　　金：国家重点基础研究发展计划(973计划,2012CB518102)~~

摘　　要：目的探讨芳香烃受体(aryl hydrocarbon receptor,AhR)内源性配体6-甲酰基吲哚并[3,2-b]咔唑(6-formylindolo[3,2-b]carbazole,FICZ)对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的保护作用及其机制。方法按照随机数字表法将24只SD大鼠分为正常对照组、FICZ对照组、LPS模型组和FICZ治疗组,每组6只。通过气管滴注LPS(3 mg/kg)制备ARDS模型,并于建模后6 h收集各组肺泡灌洗液(bronchoalveolar lavage fluid,BALF)及肺组织,通过肺湿/干质量比值、HE染色考察各组肺组织的损伤情况;采用酶联免疫吸附试验(ELISA)检测BALF和肺组织中炎症因子(IL-1β、TNF-α)水平及肺组织中髓过氧化物酶(myeloperoxidase,MPO)含量;利用Western blot检测肺组织中AhR和NF-κB p65的蛋白表达。结果与LPS模型组相比,FICZ可有效减轻LPS所致的肺水肿及组织病理学损伤,减少BALF和肺组织中炎症因子TNF-α、IL-1β的释放及肺组织中MPO的含量。另外,FICZ在激活AhR的同时对LPS作用下肺组织胞核中NF-κB p65的升高起到明显的抑制作用。结论 FICZ对LPS诱导的大鼠ARDS具有保护作用,其作用可能是通过激活AhR以减少NF-κB p65的入核来实现的。Objective To determine the protective effect of 6-formylindolo （3,2-b）carbazole （FICZ） , an endogenous ligand of aryl hydrocarbon receptor （AhR）, against lipopolysaccharide （LPS）- induced acute respiratory distress syndrome （ARDS） in rats. Methods Twenty-four adult SD rats were randomly divided into 4 groups （n = 6 per group） , that is, control group, FICZ control group, LPS model group and FICZ treatment group. ARDS model was set up via intratracheal injection of LPS （3 mg/kg）. The bronchoalveolar lavage fluid （BALF） and lung tissue were collected at 6 h after modeling. The injury of lung was characterized by wet/dry ratio and H＆E staining. The contents of inflammatory cytokines interleukin-1 beta （ IL-1 β ） and tumor necrosis factor-alpha （TNF-α） as well as myeloperoxidase （MPO） in the lung tissue and/ or BALF were determined by enzyme-linked immunosorbent assay （ELISA）. AhR and NF-KB p65 expressionin the lung tissue was detected by Western blotting. Results Compared with LPS model group, FICZ treatment significantly ameliorated LPS-induced pulmonary edema and lung tissue injury, down-regulated the levels of TNF-α and IL-1β in both BALF and lung tissue, and decreased MPO content in lung tissue. In addition, FICZ could activate AhR and remarkably suppress the LPS-induced increment of nucleic NF-κB 1365 in the necleus of lung tissue. Conclusion FICZ exerts protective effects against LPS-induced lung injury in rat ARDS model via activating AhR and suppressing NF-κB p65 nuclear translocation.

关 键 词：6甲酰基吲哚并[3 2-b]咔唑 脂多糖 急性呼吸窘迫综合征 芳香烃受体 NF-κB 

分 类 号：R-332[医药卫生] R563.8