[1]魏佳鑫,范霞,张莹,等.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[J].第三军医大学学报,2016,38(22):2419-2423.
 Wei Jiaxin,Fan Xia,Zhang Ying,et al.Protective effects of 6-formylindolo[3,2-b]carbazole against LPS-induced acute respiratory distress syndrome in rats[J].J Third Mil Med Univ,2016,38(22):2419-2423.
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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(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第22期
页码:
2419-2423
栏目:
基础医学
出版日期:
2016-11-30

文章信息/Info

Title:
Protective effects of 6-formylindolo[3,2-b]carbazole against LPS-induced acute respiratory distress syndrome in rats
作者:
魏佳鑫范霞张莹陈浩黄文娟梁华平
遵义医学院附属医院重症医学科;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
Author(s):
Wei JiaxinFan XiaZhang Ying Chen HaoHuang WenjuanLiang Huaping

Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou Povince,  563003; State Key Laboratory of Trauma, Burns and Combined Injury, Department 1, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

关键词:
6甲酰基吲哚并[32-b]咔唑脂多糖急性呼吸窘迫综合征芳香烃受体NF-&kappaB
Keywords:
6-formylindolo(32-b)carbazole lipopolysaccharide acute respiratory distress syndrome aryl hydrocarbon receptor NF-&kappaB
分类号:
R-332;R563.8;R977.6
文献标志码:
A
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(myeloperoxidase,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。

Abstract:

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-1beta (IL-1β) 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-κB p65 expression in 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 p65 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.

参考文献/References:

[1]Villar J, Fernandez R L,AmbrosA, et al. A clinical classification of the acute respiratory distress syndrome for predicting outcome and guiding medical therapy[J]. Crit Care Med. 2015,43(2): 346-353.DOI: 10.1097/CCM.000000000-0000703 
[2]Thompson B T, Moss M. A new definition for the acute respiratory distress syndrome [J]. Semin Respir Crit Care Med, 2013,34(4): 441-447. DOI: 10. 1055/s-0033-1351162
[3]Mokra D,Drgova A,Kopincova J,et al. Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconiuminduced acute lung injury[J]. Adv Exp Med Biol,2013,(756):189-196. DOI: 10.1007/97894007-4549-0_24
[4]Dinatale B C, Schroeder J C, Francey L J, et al. Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling[J]. J Biol Chem, 2010, 285(32): 24388-24397. DOI: 10.1074/jbc.M110. 118570
[5]Vogel C, Matsumura F. A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappaB family[J]. Biochem Pharmacol, 2009, 77(4): 734-745.DOI: 10.1016/j.bcp.2008.09.036
[6]Standiford T J, Ward P A. Therapeutic targeting of acute lung injury and acute respiratory distress syndrome[J]. Transl Res, 2015, 167(1): 183-191.DOI: 10.1016/j.trsl.2015.04.015
[7]Ma C H, Liu J P, Qu R, et al. Tectorigenin inhibits the inflammation of LPS-induced acute lung injury in mice [J]. Chin J Nat Med, 2014,12(11): 841-846.DOI: 10.1016/ S1875-5364(14)60126-6
[8]Zhang Y, Liang D, Dong L, et al. Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury[J]. Respir Res, 2015, 16(1): 1-13.DOI: 10.1186/s12931-015-0199-1
[9]Wincent E, Bengtsson J, Mohammadi B A, et al. Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor[J]. Proc Nati Acad Sci U S A, 2012, 109(12): 4479-4484. DOI: 10.1073/pnas.1118467109
[10]Xu T, Zhou Y, Qiu L, et al. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells[J]. J Immunol, 2015, 195(12): 5539-5550. DOI: 10.4049/ jimmunol.1501198
[11]Beamer C A, Seaver B P, Shepherd D M. Aryl hydrocarbon receptor (AhR) regulates silica-induced inflammation but not fibrosis[J]. Toxicol Sci, 2012, 126(2): 554-568. DOI: 10. 1093/toxsci/kfs024
[12]殷久恒, 韩宾, 蒲爱民,等. 6甲酰基吲哚并[3,2-b]咔唑通过下调角质细胞生长因子受体抑制结肠癌细胞增殖[J]. 第三军医大学学报, 2015(23): 2315-2319. DOI: 10.16016/j. 1000-5404.201504005
[13]Ji T, Xu C, Sun L, et al. Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis[J]. Dig Dis Sci, 2015, 60(7): 1958-1966.DOI: 10.1007/s10620-015-3632-x
[14]韩宾, 盛百伐, 张治草,等. 小鼠肠急性缺血再灌注模型中芳香烃受体活化对肠黏膜屏障功能的影响[J]. 第三军医大学学报, 2016, 38(10): 1090-1095.DOI: 10.16016/j. 1000-5404.201511153
[15]Lee Y H, Lin C H, Hsu P C, et al. Aryl hydrocarbon receptor mediates both proinflammatory and antiinflammatory effects in lipopolysaccharideactivated microglia[J]. Glia, 2015, 63(7): 1138-1154.DOI: 10. 1002/ glia.22805
[16]Vogel C F, Khan E M, Leung P S, et al. Crosstalk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB[J]. J Biol Chem, 2014, 289(3): 1866-1875.DOI: 10.1074/jbc.M113.505578
[17]Lu Y, Liu J, Li H, et al. Piperine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via, Modulating NF-κB Signaling Pathways[J]. Inflammation, 2016, 39(1): 303-308.DOI: 10.1007/s10753-015-0250-x
[18]Jiang W, Luo F, Lu Q, et al. The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state[J]. Chem Biol Interact, 2016, 243: 127-134.DOI: 10.1016/j.cbi.2015.09.010

更新日期/Last Update: 2016-11-23