切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2018, Vol. 04 ›› Issue (03) : 268 -274. doi: 10.3877/cma.j.issn.2096-1537.2018.03.011

所属专题: 文献

基础研究

神经降压素对内毒素诱导的急性肺损伤的保护作用及机制
傅水桥1,(), 骆晓倩1, 付庆辉1, 张绍阳1, 俞文桥1, 章渭方1   
  1. 1. 310000 杭州,浙江大学医学院附属第二医院
  • 收稿日期:2017-12-01 出版日期:2018-08-28
  • 通信作者: 傅水桥
  • 基金资助:
    浙江省医药卫生科技计划项目面上项目(201337952)

Protective effect of neurotensins and its mechanism in LPS-induced acute lung injury

Shuiqiao Fu1,(), Xiaoqian Luo1, Qinghui Fu1, Shaoyang Zhang1, Wenqiao Yu1, Weifang Zhang1   

  1. 1. Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310000, China
  • Received:2017-12-01 Published:2018-08-28
  • Corresponding author: Shuiqiao Fu
  • About author:
    Corresponding author: Fu Shuiqiao, Email:
引用本文:

傅水桥, 骆晓倩, 付庆辉, 张绍阳, 俞文桥, 章渭方. 神经降压素对内毒素诱导的急性肺损伤的保护作用及机制[J/OL]. 中华重症医学电子杂志, 2018, 04(03): 268-274.

Shuiqiao Fu, Xiaoqian Luo, Qinghui Fu, Shaoyang Zhang, Wenqiao Yu, Weifang Zhang. Protective effect of neurotensins and its mechanism in LPS-induced acute lung injury[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2018, 04(03): 268-274.

目的

探讨神经降压素在内毒素(LPS)所诱导的小鼠急性肺损伤(ALI)中的保护作用,并明确其在炎症反应中的作用。

方法

100只健康无特异病原级性C57BL/6小鼠(雄性50只,雌性50只),体质量(20~25 g),由上海南方模式实验动物中心提供。所有小鼠随机分为以下5组:①正常对照组:60 μl无菌磷酸缓冲盐溶液(PBS)滴鼻处理小鼠;②急性肺损伤模型组:60 μg/只LPS滴鼻处理;③20 mg/kg神经降压素组:先使用LPS诱导肺损伤,诱导后1 h通过尾静脉注射的方式给予20 mg/kg神经降压素处理;④40 mg/kg神经降压素给药组:先使用LPS诱导肺损伤,诱导后1 h通过尾静脉注射的方式给予40 mg/kg神经降压素处理;⑤80 mg/kg神经降压素给药组:先使用LPS诱导肺损伤,诱导后1 h通过尾静脉注射的方式给予80 mg/kg神经降压素处理。每组20只。肺损伤诱导后24 h,检测不同处理组小鼠肺损伤程度、髓过氧化物酶(MPO)活性、炎症细胞的浸润、肺水肿程度以及肺泡灌洗液中促炎症细胞的分泌水平。

结果

与正常对照组相比,LPS的滴鼻处理显著提高了小鼠肺组织的损伤程度,包括MPO活性、炎症细胞的浸润、肺泡灌洗液内促炎症细胞因子[肿瘤坏死因子(TNF-α)、白介素(IL)-6、IL-1b以及单核细胞趋化因子(MCP)-1]的分泌等(P<0.05);与内毒素诱导的急性肺损伤模型组相比,神经降压素的给药处理明显减轻了小鼠肺组织损伤的程度,包括MPO活性、炎症细胞的浸润、肺泡灌洗液内促炎症细胞因子(TNF-α、IL-6、IL-1b以及MCP-1)的分泌等(P<0.05),且这种保护性作用呈现剂量依赖性。

结论

神经降压素能够有效减轻由内毒素诱导的ALI,其机制可能是通过封闭由速激肽所介导的炎症反应信号通路,进而减轻内毒素引起的炎症反应对肺组织所造成的炎症损伤来实现。

Objective

To investigate the protective effect of neurotensins on inflammatory responses in mice with LPS-induced acute lung injury.

Methods

100 specific-pathogen free C57BL/6 mice (20-25 g, 6-8 weeks, 50 males and 50 females) were obtained from the Shanghai Laboratory Animal Center (SLAC) (Shanghai, China). All animals were randomly divided into five groups:① Normal control group: mice were treated with 60 μl PBS intratracheally;② LPS-induced acute lung injury group: mice were treated with 60 μg LPS intratracheally;③ 20 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and treated with 20 mg/kg Nts via tail vein injection 1 hour after LPS challenge;④ 40 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and treated with 40 mg/kg Nts via tail vein injection 1 hour after LPS challenge;⑤ 80 mg/kg neurotensins treated ALI group: mice were subjected to LPS-induced ALI and received 80 mg/kg Nts treatment via tail vein injection. The severity of lung injury, MPO acitvity, neutrophils infilatration, lung edema, and pro-inflammatory cytokines concentration in BALF were assessed 24 hours after ALI.

Results

Compared with the control group of mice, LPS induction significantly increased the severity of lung injury, including the lung edema, inflammatory cell infiltration, and the production of inflammatory cytokines in BALF (TNF-α, IL-6, IL-1β, and MCP-1). However, Neurotensins treatment obviously attenuated the lung injury caused by LPS induction, including the lung edema, the infiltration of inflammatory cells , and the secretion of inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1). Meanwhile, the protective effect is dosage dependent.

Conclusion

Neurotensins have a protective effect on LPS-induced acute lung injury in mice, and the protective mechanisms may be related to block the tachykinins mediated inflammatory pathways activation.

图1 各组小鼠肺组织病理学变化(HE,×200)
表1 各组小鼠肺脏组织中MPO、中性粒细胞数目、干湿重比以及灌洗液蛋白浓度的变化(±s
表2 各组小鼠肺泡灌洗液中TNF-α、IL-6、IL-1β及MCP-1浓度水平(pg/ml,±s
表3 各组小鼠肺泡灌洗液中COX-2和PGE2的浓度水平(U/ml,±s
图2 各组小鼠生存曲线
表4 各组小鼠生存率指标随时间变化情况(%)
1
Gotts JE,Matthay MA. Treating ARDS: new hope for a tough problem [J].Lancet Respir Med, 2014, 2(2): 84-85.
2
Matthay MA,Ware LB,Zimmerman GA. The acute respiratory distress syndrome [J]. J Clin Invest, 2012, 122(8): 2731-2740.
3
Yingkun N,Zhenyu W,Jing L, et al. Stevioside protects LPS-induced acute lung injury in mice [J]. Inflammation, 2013, 36(1): 242-250.
4
Ware LB,Matthay MA. The acute respiratory distress syndrome [J]. N Engl J Med, 2000, 342(18): 1334-1349.
5
Brun P,Mastrotto C,Beggiao E, et al. Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation [J]. Am J Physiol Gastrointest Liver Physiol, 2005, 288(4): G621-629.
6
Jiang MH,Chung E,Chi GF, et al. Substance P induces M2-type macrophages after spinal cord injury [J]. Neuroreport, 2012, 23(13): 786-792.
7
da Silva L,Neves BM,Moura L, et al. Neurotensin downregulates the pro-inflammatory properties of skin dendritic cells and increases epidermal growth factor expression [J]. Biochim Biophys Acta, 2011, 1813(10): 1863-1871.
8
Ganea D,Delgado M. Neuropeptides as modulators of macrophage functions. Regulation of cytokine production and antigen presentation by VIP and PACAP [J]. Arch Immunol Ther Exp (Warsz), 2001, 49(2): 101-110.
9
Kneyber MC,Markhorst DG. Management of acute lung injury and acute respiratory distress syndrome in children: a different perspective [J].Crit Care Med, 2009, 37(12): 3191-3192.
10
Schwab JM,Chiang N,Arita M, et al. Resolvin E1 and protectin D1 activate inflammation-resolution programmes [J]. Nature, 2007, 447(7146): 869-874.
11
Serhan CN,Krishnamoorthy S,Recchiuti A, et al. Novel anti-inflammatory--pro-resolving mediators and their receptors [J]. Curr Top Med Chem, 2011, 11(6): 629-647.
12
徐绍华,宫黎明,周满红, 等. 间充质干细胞治疗急性肺损伤的研究进展 [J/CD]. 中华危重症医学杂志(电子版), 2015, 8(6): 392-396.
13
石占利,李国辉,孙静, 等. 大黄素对重症急性胰腺炎并发急性肺损伤大鼠的干预作用 [J/CD]. 中华危重症医学杂志(电子版), 2015, 8(3): 143-149.
14
Akcan A,Muhtaroglu S,Akgun H. Ameliorative effects of bombesin and neurotensin on trinitrobenzene sulphonic acid-induced colitis, oxidative damage and apoptosis in rats [J]. World J Gastroenterol, 2008, 14(8): 1222-1230.
15
Castagliuolo I,Wang CC,Valenick L. Neurotensin is a proinflammatory neuropeptide in colonic inflammation [J]. J Clin Invest, 1999, 103(6): 843-849.
16
Margolis KG,Gershon MD. Neuropeptides and inflammatory bowel disease [J]. Curr Opin Gastroenterol, 2009, 25(6): 503-511.
17
周志毅,朱幸沨,孙洁, 等. 神经降压素受体1在大鼠肺缺血再灌注损伤中的表达及作用 [J]. 中国现代医学杂志, 2016, 26(22): 7-12.
18
Zhao D,Zhan Y,Koon HW, et al. Metalloproteinase-dependent transforming growth factor-alpha release mediates neurotensin-stimulated MAP kinase activation in human colonic epithelial cells [J]. J Biol Chem, 2004, 279(42): 43547-43554.
19
Kudoh I,Ohara M,Sawa T. Prostanoids and acute lung injury [J]. Masui, 2002, 51(6): 598-604.
20
Koon HW,Zhao D,Zhan Y, et al. Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells [J]. J Immunol, 2006, 176(8): 5050-5059.
21
赵向南. 神经降压素检测对急性颅脑损伤患者的临床意义 [J]. 河北医学, 2014, 20(2): 292-294.
[1] 李璐璐, 马利红, 金佳佳, 谷伟. 干扰素基因刺激因子通过肺巨噬细胞胞葬功能调控急性肺损伤小鼠修复的研究[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(02): 97-103.
[2] 冯芳, 陈宇, 杨静, 满珂, 蔡红燕, 李群. ω-3鱼油脂肪乳注射液在脓毒症患者中的应用:前瞻性、随机对照、先导试验[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(02): 136-139.
[3] 刘炯, 彭乐, 马伟, 江斌. 鞘外解剖肝蒂技术治疗肝内胆管细胞癌的疗效评估[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(04): 373-376.
[4] 王东阳, 林琳, 娄熙彬. SII对局部进展期胃癌nCRT+腹腔镜胃癌根治术后并发症及预后的影响研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(03): 315-318.
[5] 唐亦骁, 陈峻, 连正星, 胡海涛, 鲁迪, 徐骁, 卫强. 白果内酯对小鼠肝缺血再灌注损伤保护作用研究[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 278-282.
[6] 李智, 冯芸. NF-κB 与MAPK 信号通路及其潜在治疗靶点在急性呼吸窘迫综合征中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 840-843.
[7] 张敏龙, 杨翠平, 王博, 崔云杰, 金发光. MiR-200b-3p 通过抑制HIF-1α 表达减轻海水吸入诱导的肺水肿作用及机制[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 696-700.
[8] 廖江荣, 吴秀琳, 陈光春, 郭亮, 吕慈, 蔡俊, 陈夕. 急性主动脉夹层并发急性肺损伤的研究新进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 488-492.
[9] 李玉娟, 艾芳, 熊欢庆, 陈键, 刘刚, 李志超, 金发光. "丹蛇"组方对小鼠急性肺损伤的治疗作用[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(02): 171-177.
[10] 顾晓凌, 吴冠楠, 宋勇. 核因子E2相关因子2(Nrf2)与铁死亡在脓毒症相关急性肺损伤中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(02): 324-328.
[11] 林玲, 李京儒, 沈瑞华, 林惠, 乔晞. 基于生物信息学分析小鼠急性肾损伤和急性肺损伤的枢纽基因[J/OL]. 中华肾病研究电子杂志, 2024, 13(03): 134-144.
[12] 王子琪, 李萍, 蔡标, 杨秀敏. 雌激素在糖尿病性视网膜病变中作用机制的研究进展[J/OL]. 中华眼科医学杂志(电子版), 2024, 14(03): 187-192.
[13] 吴宗盛, 谢剑锋, 邱海波. 冷诱导RNA结合蛋白与炎症反应的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(01): 42-47.
[14] 李浩南, 张煜彭, 付焱, 冯继伟, 刘凯, 张文凯. 缝隙连接蛋白43在肺部疾病中的研究进展[J/OL]. 中华重症医学电子杂志, 2024, 10(01): 60-65.
[15] 陈雪飞, 卜雄建, 张春良. 神经内镜下经鼻蝶窦扩大鞍底入路颅咽管瘤切除术的疗效分析[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(03): 160-165.
阅读次数
全文


摘要