目的 探討血管內(nèi)皮細(xì)胞生長(zhǎng)因子( VEGF) 和腫瘤壞死因子α( TNF-α) 在大鼠肺氣腫中的作用。方法 48 只大鼠隨機(jī)分為正常對(duì)照組、肺氣腫組、rhTNFR∶Fc 干預(yù)組和假干預(yù)組。肺氣腫組、干預(yù)組和假干預(yù)組予以香煙熏吸。煙霧暴露達(dá)1 個(gè)月時(shí), 干預(yù)組予以TNF-α拮抗劑重組人Ⅱ型腫瘤壞死因子受體-抗體融合蛋白( rhTNFR∶Fc) 皮下注射, 假干預(yù)組給予空白對(duì)照制劑。熏煙80 d 后處死大鼠。大鼠肺組織切片行HE 染色觀察形態(tài)學(xué)改變。ELISA 法測(cè)定血清、BALF 中TNF-α濃度及BALF 中VEGF 濃度。結(jié)果 與正常對(duì)照組比較, 肺氣腫組肺平均內(nèi)襯間隔( MLI) 升高, 平均肺泡數(shù)( MAN) 降低, BALF中VEGF水平降低, 血清、BALF 中TNF-α濃度升高, 差異均有統(tǒng)計(jì)學(xué)意義( P lt;0. 05) 。與肺氣腫組比較, rhTNFR∶Fc 干預(yù)組MLI 無(wú)顯著差異( P gt; 0. 05) , MAN 增高( P lt; 0. 05) ;BALF 中TNF-α、VEGF 濃度無(wú)顯著差異( P gt;0. 05) , 血清中TNF-α濃度降低( P lt; 0. 05) 。肺氣腫組
BALF 中VEGF 水平與TNF-α濃度無(wú)相關(guān)性( P gt;0. 05) 。結(jié)論 VEGF 表達(dá)降低和TNF-α表達(dá)增加與吸煙大鼠的肺氣腫形成有關(guān)。VEGF與TNF-α可能各自獨(dú)立促進(jìn)肺氣腫的發(fā)生發(fā)展。
引用本文： 張程 ,張湘燕,陳平,馮端興,葉賢偉,劉維佳,韓婧. 血管內(nèi)皮細(xì)胞生長(zhǎng)因子和腫瘤壞死因子α在大鼠肺氣腫中的作用. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(4): 356-359. doi: 復(fù)制
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| 2. | Zhang C, Cai S, Chen P, et al. Inhibition of tumor necrosis factor-α reduces alveolar septal cellapoptosis in passive smoking rats. Chin Med J( Engl) , 2008, 121: 597 -601. |
| 3. | Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway.Requirement for Flk-1 /KDR activation. J Biol Chem, 1998, 273 :30336-30343 . |
| 4. | Alon T, Hemo I, Itin A, et al. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and hasimplications for retinopathy of prematurity. Nat Med, 1995, 1 : 1024 -1028. |
| 5. | Hoshino S, Yoshida M, Inoue K, et al. Cigarette smoke extract induces endothelial cell injury via JNK pathway. Biochem Biophys Res Commun, 2005, 329: 58-63. |
| 6. | Zhang J, Jin B, Li L, et al. Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. Am J Physiol Cell Physiol, 2005, 288: C840-C849. |
| 7. | 胡大為, 鮑春德, 陳順樂(lè), 等. 重組人Ⅱ 型腫瘤壞死因子受體-抗體融合蛋白治療類風(fēng)濕關(guān)節(jié)炎雙盲隨機(jī)多中心對(duì)照臨床研究.中華風(fēng)濕病學(xué)雜志, 2005, 9: 664-668. |
| 8. | Gerbitz A, Nickoloff BJ, Olkiewicz K, et al. A role for tumor necrosis factor-alpha-mediated endothelial apoptosis in the development of experimental idiopathic pneumonia syndrome. Transplantation, 2004 ,78: 494 -502. |
- 1. 王悅虹, 白春學(xué), 洪群英, 等. 血管內(nèi)皮細(xì)胞生長(zhǎng)因子及其受體在大鼠肺氣腫模型中的表達(dá). 復(fù)旦學(xué)報(bào)( 醫(yī)學(xué)版) , 2004 , 31: 488 -491.
- 2. Zhang C, Cai S, Chen P, et al. Inhibition of tumor necrosis factor-α reduces alveolar septal cellapoptosis in passive smoking rats. Chin Med J( Engl) , 2008, 121: 597 -601.
- 3. Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway.Requirement for Flk-1 /KDR activation. J Biol Chem, 1998, 273 :30336-30343 .
- 4. Alon T, Hemo I, Itin A, et al. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and hasimplications for retinopathy of prematurity. Nat Med, 1995, 1 : 1024 -1028.
- 5. Hoshino S, Yoshida M, Inoue K, et al. Cigarette smoke extract induces endothelial cell injury via JNK pathway. Biochem Biophys Res Commun, 2005, 329: 58-63.
- 6. Zhang J, Jin B, Li L, et al. Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. Am J Physiol Cell Physiol, 2005, 288: C840-C849.
- 7. 胡大為, 鮑春德, 陳順樂(lè), 等. 重組人Ⅱ 型腫瘤壞死因子受體-抗體融合蛋白治療類風(fēng)濕關(guān)節(jié)炎雙盲隨機(jī)多中心對(duì)照臨床研究.中華風(fēng)濕病學(xué)雜志, 2005, 9: 664-668.
- 8. Gerbitz A, Nickoloff BJ, Olkiewicz K, et al. A role for tumor necrosis factor-alpha-mediated endothelial apoptosis in the development of experimental idiopathic pneumonia syndrome. Transplantation, 2004 ,78: 494 -502.