目的 觀察阿魏酸鈉對(duì)肺纖維化大鼠肺組織轉(zhuǎn)化生長因子β1(TGF-β1)信號(hào)通路分子mRNA表達(dá)的影響,探討其防治肺纖維化的作用及機(jī)制。方法 氣管內(nèi)滴入博來霉素(5 mg/kg)建立大鼠肺纖維化模型。將30只SD大鼠隨機(jī)分為三組(每組10只):對(duì)照組、肺纖維化模型組和阿魏酸鈉組。HE染色檢測(cè)肺組織病理改變,膠原纖維染色檢測(cè)膠原纖維表達(dá),原位雜交技術(shù)檢測(cè)肺組織TGF-βRⅡ及Smad4 mRNA表達(dá),實(shí)時(shí)熒光定量RT-PCR技術(shù)檢測(cè)TGF-β1 mRNA表達(dá)。結(jié)果 膠原纖維染色顯示模型組大鼠肺內(nèi)膠原纖維表達(dá)顯著高于對(duì)照組和阿魏酸鈉組(P lt;0.001)。大鼠肺內(nèi)TGF-β1、TGF-βRⅡ和Smad4的mRNA表達(dá)在模型組顯著高于對(duì)照組(P lt;0.01),在阿魏酸鈉組顯著低于模型組(P lt;0.05)。結(jié)論 阿魏酸鈉能有效地減輕肺纖維化大鼠肺組織的纖維化程度,其作用機(jī)制主要是通過抑制TGF-β1、TGF-βRⅡ和Smad4的mRNA表達(dá)上調(diào),從而干擾TGF-β1/Smad4信號(hào)通路對(duì)靶基因的激活來實(shí)現(xiàn)的。
引用本文: 穆茂,程德云,楊禮騰,方詢,聶莉,胡小波. 阿魏酸鈉對(duì)肺纖維化大鼠肺組織轉(zhuǎn)化生長因子β1信號(hào)通路分子mRNA表達(dá)的影響. 中國呼吸與危重監(jiān)護(hù)雜志, 2007, 6(2): 110-113. doi: 復(fù)制
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1. | Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:410-411. |
2. | 賀德,曾志良,曹建華,等.阿魏酸鈉抗大鼠肝纖維化.世界華人消化雜志,2002,10:240-241. |
3. | 陳輝珍,樊均明.阿魏酸鈉與腎間質(zhì)纖維化關(guān)系的探討.中藥新藥與臨床藥理,2003,14:353-355. |
4. | 王伯沄,李玉松,黃高異,主編.病理學(xué)技術(shù).北京:人民衛(wèi)生出版社,2000:142-144. |
5. | Weller SA.,Elphinstone JG,Smith NC,et al.Detection of Ralstonia solanacearum strains with a quantitative,multiplex,real-time,fluorogenic PCR (TaqMan) assay.Appl Environ Microbiol,2000,66:2853-2858. |
6. | Clark JG,Kostal KM,Marino BA.Bleomycin-induced pulmonary fibrosis in hamsters.An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.J Clin Invest,1983,72:2082-2091. |
7. | 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達(dá)對(duì)不同時(shí)期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國呼吸與危重監(jiān)護(hù)雜志,2005,4:130-134. |
8. | 馬躍文,侯顯明,康健,等.轉(zhuǎn)化生長因子β1及其Ⅰ、Ⅱ型受體在肺纖維化組織中的表達(dá)變化和意義.中華結(jié)核和呼吸雜志,2000,23:701-702. |
9. | 徐曉峰,王辰,代華平,等.大鼠肺纖維化過程中轉(zhuǎn)化生長因子β1及其受體的同相表達(dá).中華結(jié)核和呼吸雜志,2002,25:550-551. |
10. | 劉濤,宋良文.肺纖維化發(fā)生的分子機(jī)制和早期防治研究進(jìn)展.軍事醫(yī)學(xué)科學(xué)院院刊,2003,27:312-316. |
11. | Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:431-435. |
12. | Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765. |
13. | Wrana JL,Attisano L,Wieser R,et al.Mechanism of activation of the TGF-beta receptor.Nature,1994,370:341-347. |
14. | Heldin CH,Miyazono K,ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature,1997,390:465-471. |
15. | Correia JJ,Chacko BM,Lam SS,et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3:Smad4 homo- and hetero-trimerization.Biochemistry,2001,40:1473-1482. |
16. | 廖丹,江建寧.肝纖維化形成的機(jī)制——信號(hào)轉(zhuǎn)導(dǎo)通路TGF-β/Smad的作用概論.國外醫(yī)學(xué)(流行病學(xué)與傳染病學(xué)分冊(cè)),2004,31:170-172. |
17. | Zhang W,Ou J,Inagaki Y,et al.Synergistic cooperation between Spl and Smad3/Smad4 mediates transforming growth factor betal stimulation of alpha2(I)-collagen (COLIA2) transcription.J Biol Chem,2000,275:39237-39245. |
18. | Ghosh AK,Yuan W,Mori Y,et al.Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth facter-beta.Integration at the level of p300/CBP transcriptional coactivators.J Biol Chem,2001,276:11041-11048. |
19. | 劉向峰,李娜.阿魏酸鈉的臨床應(yīng)用.寧夏醫(yī)學(xué)雜志,2005,27:69-70. |
20. | 黃瑾,胡晉紅,邱磊,等.阿魏酸鈉抑制肝星狀細(xì)胞合成膠原的機(jī)制.藥學(xué)學(xué)報(bào),2004,39:577 -580. |
- 1. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:410-411.
- 2. 賀德,曾志良,曹建華,等.阿魏酸鈉抗大鼠肝纖維化.世界華人消化雜志,2002,10:240-241.
- 3. 陳輝珍,樊均明.阿魏酸鈉與腎間質(zhì)纖維化關(guān)系的探討.中藥新藥與臨床藥理,2003,14:353-355.
- 4. 王伯沄,李玉松,黃高異,主編.病理學(xué)技術(shù).北京:人民衛(wèi)生出版社,2000:142-144.
- 5. Weller SA.,Elphinstone JG,Smith NC,et al.Detection of Ralstonia solanacearum strains with a quantitative,multiplex,real-time,fluorogenic PCR (TaqMan) assay.Appl Environ Microbiol,2000,66:2853-2858.
- 6. Clark JG,Kostal KM,Marino BA.Bleomycin-induced pulmonary fibrosis in hamsters.An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.J Clin Invest,1983,72:2082-2091.
- 7. 徐鈺,高占成,陳彬,等.γ-干擾素轉(zhuǎn)基因表達(dá)對(duì)不同時(shí)期博萊霉素致小鼠肺間質(zhì)纖維化的作用.中國呼吸與危重監(jiān)護(hù)雜志,2005,4:130-134.
- 8. 馬躍文,侯顯明,康健,等.轉(zhuǎn)化生長因子β1及其Ⅰ、Ⅱ型受體在肺纖維化組織中的表達(dá)變化和意義.中華結(jié)核和呼吸雜志,2000,23:701-702.
- 9. 徐曉峰,王辰,代華平,等.大鼠肺纖維化過程中轉(zhuǎn)化生長因子β1及其受體的同相表達(dá).中華結(jié)核和呼吸雜志,2002,25:550-551.
- 10. 劉濤,宋良文.肺纖維化發(fā)生的分子機(jī)制和早期防治研究進(jìn)展.軍事醫(yī)學(xué)科學(xué)院院刊,2003,27:312-316.
- 11. Xaubet A,Marin-Arguedas A,Lario S,et al.Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis.Am J Respir Crit Care Med,2003,168:431-435.
- 12. Bartram U,Speer CP.The role of transforming growth factor beta in lung development and disease.Chest,2004,125:754-765.
- 13. Wrana JL,Attisano L,Wieser R,et al.Mechanism of activation of the TGF-beta receptor.Nature,1994,370:341-347.
- 14. Heldin CH,Miyazono K,ten Dijke P.TGF-β signaling from cell membrane to nucleus through SMAD proteins.Nature,1997,390:465-471.
- 15. Correia JJ,Chacko BM,Lam SS,et al.Sedimentation studies reveal a direct role of phosphorylation in Smad3:Smad4 homo- and hetero-trimerization.Biochemistry,2001,40:1473-1482.
- 16. 廖丹,江建寧.肝纖維化形成的機(jī)制——信號(hào)轉(zhuǎn)導(dǎo)通路TGF-β/Smad的作用概論.國外醫(yī)學(xué)(流行病學(xué)與傳染病學(xué)分冊(cè)),2004,31:170-172.
- 17. Zhang W,Ou J,Inagaki Y,et al.Synergistic cooperation between Spl and Smad3/Smad4 mediates transforming growth factor betal stimulation of alpha2(I)-collagen (COLIA2) transcription.J Biol Chem,2000,275:39237-39245.
- 18. Ghosh AK,Yuan W,Mori Y,et al.Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth facter-beta.Integration at the level of p300/CBP transcriptional coactivators.J Biol Chem,2001,276:11041-11048.
- 19. 劉向峰,李娜.阿魏酸鈉的臨床應(yīng)用.寧夏醫(yī)學(xué)雜志,2005,27:69-70.
- 20. 黃瑾,胡晉紅,邱磊,等.阿魏酸鈉抑制肝星狀細(xì)胞合成膠原的機(jī)制.藥學(xué)學(xué)報(bào),2004,39:577 -580.