Lung Tissue Apoptosis Mechanism of LPS-induced ARDS in Mice <i>via</i> TNF-α Neutralization_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhangAnbing ^1,2 , LiLi ¹ , YuanWeifeng ¹ , XianJun ¹ ,  HuangWenjie ¹

1. Department of Respiratory Medicine, Guangzhou Military General Hospital, Guangzhou, Guangdong, 510010, China;
2. ;

Corresponding author：

HuangWenjie, Email: Huangyelu1029@vip.163.com

Keywords：

Acute respiratory distress syndrome; Lipopolysaccharide; Tumor necrosis factor-alpha; Apoptosis

DOI：

10.7507/1671-6205.2014059

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Objective To investigate the mechanism of lung tissue apoptosis in LPS-induced mice ARDS via TNF-α neutralization. Methods Thirty-six mice were randomly divided into a control group,a LPS group,and TNF-α neutralization group.LPS(5 mg/kg) was intratracheally nebulized to induce ARDS in the LPS group and the TNF-α neutralization group.Twenty-four hours before LPS treatment,etanercept (0.4 mg/kg) was abdominal injected to the mice in the TNF-α neutralization group.Mice were sacrificed 2 hours after LPS treatment.PCR were used to detected the expression of NF-κB p65,Bax and Bcl-2 in lung tissue.Western blot were used to detected protein level of NF-κB p65,Erk1/2 and their phosphorylation and Bax,Bcl-2.The lung dry-to-wet ratio was measured.The lung histological changes were evaluated by HE staining. Results Activation level of NF-κB p65 and Erk1/2 was elevated,the ratio of Bcl-2 and Bax was decreased in the LPS group(P<0.05).After TNF-α neutralization,the activation level of NF-κB p65 and Erk1/2 were reduced,the ratio of Bcl-2 and Bax was increased (P<0.05).Compared with the LPS group,the lung dry-to-wet ratio and lung injury semi-quantitative score were significantly decreased in the TNF-α neutralization group (P<0.05). Conclusion TNF-α neutralization can suppress lung injury in LPS-induced ARDS mice by inhibiting activation of NF-κB p65 and Erk1/2,increasing the ratio of Bcl-2 and Bax ratio,and eventually reducing apoptosis.

Citation： ZhangAnbing, LiLi, YuanWeifeng, XianJun, HuangWenjie. Lung Tissue Apoptosis Mechanism of LPS-induced ARDS in Mice via TNF-α Neutralization. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(3): 246-249. doi: 10.7507/1671-6205.2014059 Copy

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1. Frutos-Vivar F,Nin N,Esteban A.Epidemiology of acute lung injury and acute respiratory distress syndrome.Curr Opin Crit Care,2004,10:1-6.
2. Mukhopadhyay S,Hoidal JR,Mukherjee TK.Role of TNFalpha in pulmonary pathophysiology.Respir Res,2006,7:125.
3. 袁伟锋,李理,李跃飞,等.TNF-α中和对脂多糖致急性肺损伤小鼠肺组织凋亡的影响.国际呼吸杂志,2012,32:565-568.
4. Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits.Anesth Analg,2003,97:1751-1755.
5. Miakotina OL,Snyder JM.TNF-alpha inhibits SP-A gene expression in lung epithelial cells via p38 MAPK.Am J Physiol Lung Cell Mol Physiol,2002,283:L418-L427.
6. Raymondos K,Martin MU,Schmudlach T,et al.Early alveolar and systemic mediator release in patients at different risks for ARDS after multiple trauma.Injury,2012,43:189-195.
7. Schütte H,Lohmeyer J,Rosseau S,et al.Bronchoalveolar and systemic cytokine profiles in patients with ARDS,severe pneumonia and cardiogenic pulmonary oedema.Eur Respir J,1996,9:1858-1867.
8. 陈成,黄建安.急性肺损伤/急性呼吸窘迫综合征预后评估指标研究进展.中国呼吸与危重监护杂志,2008,7:81-85.
9. Salminen A,Kaarniranta K.Glycolysis links p53 function with NF-kappaB signaling:impact on cancer and aging process.J Cell Physiol,2010,224:1-6.
10. Xu G,Gong Z,Yu W,et al.Increased expression ratio of Bcl-2/Bax is associated with crocin-mediated apoptosis in bovine aortic endothelial cells.Basic Clin Pharmacol Toxicol,2007,100:31-35.
11. 刘庆辉,刘长庭,石敏,等.重组人促红细胞生成素对成年大鼠高氧肺损伤Bax和Bcl-2蛋白表达的影响.中国呼吸与危重监护杂志,2011,10:346-349.
12. Dent P,Yacoub A,Fisher PB,et al.MAPK pathways in radiation responses.Oncogene,2003,22:5885-5896.
13. Dutta J,Fan Y,Gupta N,et al.Current insights into the regulation of programmed cell death by NF-κB.Oncogene,2006,25:6800-6816.

Chinese Journal of Respiratory and Critical Care Medicine

Lung Tissue Apoptosis Mechanism of LPS-induced ARDS in Mice via TNF-α Neutralization

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