p38MAPK信号通路在猪源H9N2流感病毒导致小鼠肺损伤中作用的研究

doi:10.11843/j.issn.0366-6964.2014.02.017

畜牧兽医学报 ›› 2014, Vol. 45 ›› Issue (2): 281-288.doi: 10.11843/j.issn.0366-6964.2014.02.017

p38MAPK信号通路在猪源H9N2流感病毒导致小鼠肺损伤中作用的研究

王存连，魏东，徐明举，张瑞华，刘宝剑，王国华，田树飞，徐彤^*

（河北北方学院预防兽医学重点实验室，宣化 075131）

收稿日期:2013-07-03 出版日期:2014-02-23 发布日期:2014-03-07
通讯作者: 徐彤（1969-），男，博士，教授，硕士生导师，E-mail：xutong1969@sohu.com
作者简介:王存连(1968-)，女，高级实验师，学士，主要从事基础兽医学研究，E-mail：zgnd_2003@163.com
基金资助:
河北省自然基金 (C2011405002)；河北省教育厅重点课题(ZD20131045)；河北北方学院校级重大课题(ZD201306)

The Role of p38MAPK in Acute Lung Injury Induced by H9N2 Influenza Virus Isolated from Swine

WANG Cun-lian，WEI Dong，XU Ming-ju，ZHANG Rui-hua，LIU Bao-jian，WANG Guo-hua，TIAN Shu-fei，XU Tong^*

(Key Laboratory of Preventive Veterinary Medicine of Hebei North University，Xuanhua 075131，China)

Received:2013-07-03 Online:2014-02-23 Published:2014-03-07

摘要/Abstract

摘要：

探讨p38MAPK信号通路在猪源H9N2流感病毒诱导小鼠肺损伤过程中的作用。将BALB/c小鼠随机分为病毒感染组(H9N2组)、模拟感染组（NS组）和H9N2+p38MAPK抑制剂组（H9N2+SB203580）。Western blot方法检测肺组织p38MAPK表达，观察各组小鼠肺组织病理学变化、测定肺湿/干重比，衡量肺损伤情况；同时进行支气管肺泡灌洗液（BALF）内细胞计数和肿瘤坏死因子α（TNF-α）及白细胞介素-1β(IL-1β)的测定。结果如下：Western blot结果显示感染组小鼠肺组织内p38MAPK表达显著高于H9N2+SB203580抑制剂组(P<0.01)；感染组小鼠精神沉郁、呼吸困难、体重下降；肺组织学表现为肺泡间质水肿、炎性细胞渗出、出血为特征的弥漫性肺泡损伤。与感染组相比，p38MAPK抑制剂组症状较轻，一定程度上降低了死亡率，并明显延长小鼠存活时间(P<0.01)；同时，小鼠BALF内炎性细胞渗出减少，TNF-α和IL-1β的含量 (P<0.05)以及肺湿/干重较感染组显著下降 (P<0.01)。本研究证实p38MAPK信号通路参与H9N2流感病毒诱导小鼠肺损伤过程，其抑制剂SB203580能够有效减少p38MAPK表达，进而减少TNF-α和IL-1β产生以及炎性细胞渗出，缓解肺损伤的严重程度，延长小鼠存活时间和降低死亡率，提示p38MAPK信号通路抑制剂SB203580在今后作为辅助预防和干预H9N2-SIV诱导肺损伤具有一定的应用前景。

关键词: 猪源H9N2流感病毒, 急性肺损伤, p38MAPK, SB203580

Abstract:

The aim of this study was to investigate the role of p38MAPK in acute lung injury (ALI) induced by H9N2 influenza virus isolated from swine (H9N2-SIV) in mouse model.BALB/c mice were divided into H9N2 infected group，H9N2 + p38MAPK inhibitor (SB203580) group and mock infected group.The lungs were observed for lesion of pathological change and the lung wet weight/dry weight (W/D) were investigated; The quantity of MAP kinases protein were detected by Western blot analysis; The cell count and the contents of TNF-α and IL-1β in bronchial alveolar lavaged fluid (BALF) were measured.The results were as follows：the result of western blot showed that the quantity of MAP kinases protein in lung of H9N2 group higher significantly compared with H9N2 + SB203580 group (P<0.01); Furthermore，depression，dyspnea and weight loss appeared on H9N2 infected mice markedly; Histopathologically，the similar histopathological changes such as alveolar and interstitial edema，hemorrhage，inflammation cell infiltration were also observed in lung in H9N2 + SB203580 group mice，but the degree of lung lesions was not as serious as those in H9N2 group; Moreover，the interventions of SB203580 decreased the morality of infected mice (P<0.01)，and prolonged the survival time of infected mice significantly.Meanwhile，it also decreased markedly W/D（wet weight/dry weight of lung），the number of inflammatory cell and levels of TNF-α and IL-1β in BALF (P<0.01).The results indicated that p38MAPK had an important role in the process of H9N2-SIV-induced ALI，and its inhibors SB203580 may block effectively expression of p38MAPK，and ameliorate lung injuries by inhibiting excessive discharging of TNF-α and IL-1β，which suggesting that SB203580 have benefit role to intervene the ALI induced by H9N2-SIV influenza virus in future.

Key words: H9N2 swine influenza, acute lung injury, p38MAPK, SB203580

中图分类号:

S855.3

王存连，魏东，徐明举，张瑞华，刘宝剑，王国华，田树飞，徐彤. p38MAPK信号通路在猪源H9N2流感病毒导致小鼠肺损伤中作用的研究[J]. 畜牧兽医学报, 2014, 45(2): 281-288.

WANG Cun-lian，WEI Dong，XU Ming-ju，ZHANG Rui-hua，LIU Bao-jian，WANG Guo-hua，TIAN Shu-fei，XU Tong. The Role of p38MAPK in Acute Lung Injury Induced by H9N2 Influenza Virus Isolated from Swine[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2014, 45(2): 281-288.

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p38MAPK信号通路在猪源H9N2流感病毒导致小鼠肺损伤中作用的研究

The Role of p38MAPK in Acute Lung Injury Induced by H9N2 Influenza Virus Isolated from Swine

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