目的 探討糖皮質(zhì)激素對(duì)慢性支氣管炎大鼠氣道炎癥的抑制作用, 并觀察其對(duì)氣道磷酸二酯酶4D( PDE4D) 和TNF-α表達(dá)的影響, 探討其作用機(jī)制。方法 雄性SD 大鼠40 只隨機(jī)分為5組, 每組8 只。吸煙組: 香煙煙霧吸入法建立慢性支氣管炎模型; 甲基潑尼松龍( 甲強(qiáng)龍) 低劑量干預(yù)組和高劑量干預(yù)組: 每日吸入煙霧之前分別給予腹腔內(nèi)注射甲強(qiáng)龍1 mg/kg和10 mg/ kg, 1 次/d。同時(shí)設(shè)空白對(duì)照組( 不予任何處理) 和甲強(qiáng)龍對(duì)照組( 每日給予甲強(qiáng)龍10 mg/ kg 腹腔注射) 。采用免疫組化法檢測(cè)氣管及肺氣道上皮PDE4D表達(dá)的變化, 以灰度掃描和圖像分析測(cè)定PDE4D陽(yáng)性染色的平均吸光度; 收集BALF 進(jìn)行細(xì)胞計(jì)數(shù)及分類, ELISA法檢測(cè)BALF 中TNF-α和IL-8 濃度的變化。結(jié)果 香煙煙霧致大鼠慢性支氣管炎形成, 甲強(qiáng)龍低劑量組和高劑量組大鼠氣管及各級(jí)支氣管炎性細(xì)胞聚集、上皮細(xì)胞腫脹及漿液滲出均減輕。與對(duì)照組相比, 吸煙顯著增加大鼠氣管與肺組織氣道黏膜上皮
PDE4D的表達(dá), 且PDE4D表達(dá)增加與BALF 中TNF-α和IL-8 釋放量增加呈正相關(guān)。甲強(qiáng)龍干預(yù)后,PDE4D蛋白表達(dá)減低, BALF中TNF-α和IL-8 釋放減少; 增大甲強(qiáng)龍劑量, PDE4D、TNF-α和IL-8 水平進(jìn)一步降低, 以上差異均具有統(tǒng)計(jì)學(xué)意義( P lt;0. 05) ; 高劑量甲強(qiáng)龍對(duì)中性粒細(xì)胞數(shù)量和TNF-α濃度的影響與低劑量甲強(qiáng)龍相比無(wú)顯著差異( P gt;0. 05) 。結(jié)論 甲強(qiáng)龍抑制氣道上皮PDE4D的表達(dá), 進(jìn)而下調(diào)吸煙介導(dǎo)的TNF-α產(chǎn)物, 從而有利于減少炎癥細(xì)胞的聚集, 有效減輕慢性支氣管炎大鼠支氣管黏膜的充血、水腫。
引用本文： 李莉,王向東. 糖皮質(zhì)激素抑制慢性支氣管炎大鼠氣道磷酸二酯酶4D和腫瘤壞死因子α的表達(dá). 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(6): 534-538. doi: 復(fù)制
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| 2. | Tang HF, Song YH, Chen JC, et al. Upregulation of Phosphodiesterase-4 in the lung of allergic rats. Am JRespire Crit Care Med,2005, 171: 823-828. |
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| 6. | 廖秀清, 宋云熙, 王彥, 等. 西洛司特對(duì)COPD 患者PBMC 分泌IL-8 和TNF-α的影響. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2006, 28: 257-259. |
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| 8. | Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol, 2006, 533: 110-117. |
| 9. | 鄭緒陽(yáng), 謝強(qiáng)敏, 杜曉剛, 等. 大鼠急性肺損傷模型肺組織中磷酸二酯酶4 活性的變化. 中國(guó)藥理學(xué)通報(bào), 2006, 22: 844-848. |
| 10. | Jin SL, Conti M. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci USA, 2002, 99: 7628-7633. |
| 11. | Hamamoto M, Suga M, Nakatani T, et al. Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model. Eur J Cardiot horac Surg, 2004,25 : 833-838. |
| 12. | Ouagued M, Chouly CA, Brinchault G, et al. The novel phosphodiesterase 4 inhibitor. CI-1044. inhibits LPS- induced TNF-α production in whole blood from COPD patients. Pulm Pharmacol Ther, 2005, 18: 49-54. |
- 1. Sherrill DL, Holberg CJ, Enright PL, et al. Longitudinal analysis of the effects of smoking onset and cessation on pulmonary function.Am J Respir Crit Care Med, 1994, 149: 591-597.
- 2. Tang HF, Song YH, Chen JC, et al. Upregulation of Phosphodiesterase-4 in the lung of allergic rats. Am JRespire Crit Care Med,2005, 171: 823-828.
- 3. Aggarwal BB, Kohr WJ, Hass PE, et al. Human tumor necrosis factor: production, purification, and characferization. J Biol Chem,1985, 260: 2345-2354.
- 4. 童旭峰, 劉進(jìn), 管彩虹, 等. 用被動(dòng)吸煙的方法建立慢性支氣管炎大鼠模型及研究. 中華綜合醫(yī)學(xué), 2002, 3: 484-485.
- 5. Aaron SD, Angel JB, Lunan M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001 ,163: 349-355.
- 6. 廖秀清, 宋云熙, 王彥, 等. 西洛司特對(duì)COPD 患者PBMC 分泌IL-8 和TNF-α的影響. 第三軍醫(yī)大學(xué)學(xué)報(bào), 2006, 28: 257-259.
- 7. Crocker IC, Townley RG. Therapeutic potential of phosphodiesterase 4 inhibitors in allergic diseases. Drugs Today, 1999, 35: 519-535.
- 8. Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol, 2006, 533: 110-117.
- 9. 鄭緒陽(yáng), 謝強(qiáng)敏, 杜曉剛, 等. 大鼠急性肺損傷模型肺組織中磷酸二酯酶4 活性的變化. 中國(guó)藥理學(xué)通報(bào), 2006, 22: 844-848.
- 10. Jin SL, Conti M. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci USA, 2002, 99: 7628-7633.
- 11. Hamamoto M, Suga M, Nakatani T, et al. Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model. Eur J Cardiot horac Surg, 2004,25 : 833-838.
- 12. Ouagued M, Chouly CA, Brinchault G, et al. The novel phosphodiesterase 4 inhibitor. CI-1044. inhibits LPS- induced TNF-α production in whole blood from COPD patients. Pulm Pharmacol Ther, 2005, 18: 49-54.