Expression of nuclear factor kappa B in rat model of chronic obstructive pulmonary disease and the efect of glucocorticoid_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GUAN Jian ^1# , ZHENG Bixia ² ,  CHENG Deyun. ¹

Department of Respiratory Medecine，West China Hospital，Sichan University, Chengdu，Sichuan，610041，China Corresponding author: CHENG De-yun，E-mail：chengdeyun@sohu.com;

Corresponding author：

CHENG Deyun., Email: chengdeyun@sohu.com

Keywords：

Chronic obstructive pulmonary disease; Nuclear factor kappa B; Airway inflammation; Prednisone

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Objective To explore the role of nuclear factor kappa B(NF-KB)in the pathogenesis of chronic obstructive pulmonary disease(COPD)and the therapeutic efects of glucocorticoid．Methods Twenty-four Wistar rats were randomly divided into three groups，ie．normal control，COPD model and prednisone preventive treatment group．Rat COPD model Was established by exposing the rats to cigarette smoke daily．Prednisone Was given through stomachal injection on altemate days．After COPD model Was set up，bronchoalveolar lavage(BAL)Was performed．Total cell counts and neutrophil counts in BALF were examined．Pathological changes of lung tissue Was observe0 by hematoxylin-eosin staining．The morphological indices of pulmonary emphysema(MLI，MAN and PAA)Was measured by a computerized
image analyzer and compared in three groups．NF-KB expression in lung tissues were detected by immunohistochemistry assay．Rults Emphysema Was confirmed by three morphological indices in COPD model group compared to those of normal control group[MLI：(97.97±11.10)×10-6m vs (47．23±2．80)×10-6 m，MAN：(95.98±l4.89)×106 ／m vs (164.21±9．30)×106 ／m ，PAA：(64 ±5.7)％vs (44±2.7)％，P lt;0.01]．Total cell counts and neutrophil counts in BALF of COPD model group were significantly higher than those of control group[（5.76±0.29）×108/L vs （1.64±0.12）×108/L，（1.26±0.25）×108/L vs （0.099±0.065）×108/L，P lt;0.01]．After the preventive treatment with prednisone，MLI，MAN and PAA were significantly changed[（57.66±4.62）×10－6mvs （97.97±11.10）×10－6m，（111.40±16.92）×106个/m2 vs （95.98±14.89）×106个/m2，P lt;0.01；（58±6.1）% vs （64±5.7）%，P lt;0.05]，which indicated that airway inflammation and emphysematous injury in preventive treatm ent group were milder than those of COPD mode1．Total ceil counts and neutrophil counts
in BALF were found in preventive treatment group as compared to those of COPD model[[（3.18±0.29）×108/L vs （5.76±0.29）×108/L，（0.57±0.12）×108/L vs （1.26±0.25）×108/L，P lt;0.01].The percentage of positive cells of NF-KB nuclear staining in bronchiolar epithelial ceils was significantly increased in the COPD group than that in the control group[（29.02±1.25）% vs （12.17±1.13）%，P lt;0.01]，but was significantly decreased in the preventive treatment group[(19.23±1.18)％vs (29.02±1.25)％，P lt;0．01]．Conclusions NF-KB may be responsible for the persistence and amplification of inflammation in COPD through neutrophil recruitment and activation．Prednisone may suppress airwayinflammation in COPD by inhibiting NF-KB．

Citation： GUAN Jian ,ZHENG Bixia,CHENG Deyun.. Expression of nuclear factor kappa B in rat model of chronic obstructive pulmonary disease and the efect of glucocorticoid. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(1): 52-56. doi: Copy

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1. Pauwels RA ， Buist AS ， Calverley PM ，et al.Global strategy for the diagnosis，management，and prevention of chronic obstructive pulmonary disease.NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.Am J Respir Crit Care Med，2001，163：1256-1276.
2. Christman JW，Sadikot RT，Blackwell TS.The role of nuclear factor-kappa B in pulmonary diseases.Chest，2000，117：1482-1487.
3. Sen R，Baltimore D.Multiple nuclear factors interact with the immunoglobulin enhancer sequences.Cell，1986，46：705-716.
4. Blackwell TS，Christman JW.The role of nuclear factor-kappa B in cytokine gene regulation.Am J Respir Cell Mol Biol，1997，17：3-9.
5. Mio T，Romberger DJ，Thompson AB，et al.Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells.Am J Respir Crit Care Med，1997，155：1770-1776.
6. 张永，程德云，王慧，等.慢性阻塞性肺疾病大鼠肺内IL-8和TNF-α与气道炎症的关系研究.中国呼吸与危重监护杂志，2003，2：355-358.
7. Barnes PJ，Adcock IM.Glucocorticoid receptors.In：Crystal，et al.The lung：scientific foundations.2d ed.Philadelphia，Pa：Lippincott-Raven，1997，37-55.
8. John M，Au BT，Jose PJ，et al.Expression and release of interleukin-8 by human airway smooth muscle cells：inhibition by Th-2 cytokines and corticosteroids.Am J Respir Cell Mol Biol，1998，18：84-90.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of nuclear factor kappa B in rat model of chronic obstructive pulmonary disease and the efect of glucocorticoid

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