目的 探討核因子KB(NF-KB)在慢性阻塞性肺疾病(COPD)發(fā)病機(jī)制中的作用及糖皮質(zhì)激素在COPD中的治療價(jià)值。方法 Wistar大鼠24只隨機(jī)分為3組:對(duì)照組、COPD組和激素組,每組8只大鼠。采用單純熏香煙法建立COPD模型,激素組于熏香煙前予潑尼松隔日灌胃。支氣管肺泡灌洗(BAL),測(cè)定支氣管肺泡灌洗液(BALF)中細(xì)胞總數(shù)、中性粒細(xì)胞絕對(duì)計(jì)數(shù)和百分比,并對(duì)肺組織切片行HE染色觀察形態(tài)學(xué)改變,采用圖像分析系統(tǒng)定量測(cè)定肺平均內(nèi)襯間隔(MLI)、平均肺泡數(shù)(MAN)和肺泡腔面積與總面積比(PAA)。對(duì)大鼠肺組織切片采用免疫組織化學(xué)法觀察3組大鼠肺組織NF.KB表達(dá)的變化。結(jié)果 COPD組MLI和PAA均較對(duì)照組增高,差異有統(tǒng)計(jì)學(xué)意義(P lt;0.01),潑尼松干預(yù)后下降(與COPD組比較,P lt;0.01或0.05),而COPD組MAN低于對(duì)照組,治療后增高,差異有統(tǒng)計(jì)學(xué)意義(P lt;0.01或0.05)。與對(duì)照組比較,COPD組BALF中白細(xì)胞總數(shù)[(1.64±0.12)×108/L比(5.76±0.29)×108/L]、中性粒細(xì)胞絕對(duì)計(jì)數(shù)[(0.099±0.065)×108 /L比(1.26±0.25)×108 /L]均增高,差異有統(tǒng)計(jì)學(xué)意義(P lt;0.01)。潑尼松干預(yù)后上述指標(biāo)均下降(P lt;0.01)。COPD組細(xì)支氣管上皮細(xì)胞NF-KB核染色陽(yáng)性細(xì)胞百分比為(29.02±1.25)%,與正常組[(12.17±1.13)%]比較,差異有統(tǒng)計(jì)學(xué)意義(P lt;0.01);激素組為(19.23±1.18)%,與COPD組比較,差異亦有統(tǒng)計(jì)學(xué)意義(P lt;0.01)。結(jié)論 NF-KB與COPD的氣道炎癥密切相關(guān),潑尼松治療可以通過(guò)調(diào)節(jié)NF.KB的表達(dá),抑制粒細(xì)胞趨化和脫顆粒,增加中性粒細(xì)胞彈性蛋白酶的抑制活性,從而減輕氣道炎癥及其對(duì)氣道的損害,延緩COPD的進(jìn)展。
引用本文: 關(guān)鍵 ,鄭碧霞,程德云. 核因子-κB在慢性阻塞性肺疾病大鼠肺內(nèi)的表達(dá)及潑尼松對(duì)其的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2008, 08(1): 52-56. doi: 復(fù)制
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. | 張永,程德云,王慧,等.慢性阻塞性肺疾病大鼠肺內(nèi)IL-8和TNF-α與氣道炎癥的關(guān)系研究.中國(guó)呼吸與危重監(jiān)護(hù)雜志,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. |
- 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. 張永,程德云,王慧,等.慢性阻塞性肺疾病大鼠肺內(nèi)IL-8和TNF-α與氣道炎癥的關(guān)系研究.中國(guó)呼吸與危重監(jiān)護(hù)雜志,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.