Role of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Pathogenesis of Emphysema ZHANG Cheng*_Chinese Journal of Respiratory and Critical Care Medicine

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Department of Respiratory Medicine, Guizhou Provincial People’s Hospital. Guiyang, Guizhou,550002, ChinaCorresponding Author: ZHANG Xiang-yan, E-mail: zxy35762@ 126. com;

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Keywords：

Recombinant fusion proteins; Emphysema; Vascular endothelial growth factor; Tumor necrosis factor alpha

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Objective To investigate the role of vascular endothelial growth factor ( VEGF) in the pathogenesis of emphysema and its relationship with tumor necrosis factor alpha ( TNF-α) . Methods 48 rats were randomly divided into four groups, ie. a normal control group, an emphysema group, a rhTNFR∶Fc intervention group, and a sham intervention group. The rats in the emphysema group, the rhTNFR: Fc intervention group, and the shamintervention group were exposed to cigarette smoking for 80 days. After 30 days of exposure, rhTNFR: Fc hypodermic injection was administered in the rhTNFR: Fc intervention group while placebo was injected in the sham intervention group as control. Lung tissue sections were stained by hematoxylin and eosin. Mean linear intercept ( MLI) and mean alveolar numbers ( MAN) were measured to estimate the extent of emphysema. The level of TNF-αin serumand BALF, and the level of VEGF in BALF were measured with ELISA. Results In the emphysema group, MLI was higher and MAN was lower than those in the normal control group. Moreover, the levels of TNF-αin serum and BALF were higher, and the
level of VEGF in BALF was lower significantly ( P lt;0. 05) . After the intervention with rhTNFR∶Fc, MAN increased and the serum TNF-αdecreased significantly compared with the emphysema group ( P lt; 0. 05) .However there were no significant differences in MLI, VEGF, and TNF-α in BALF ( P gt; 0. 05 ) . No correlation was found between the level of TNF-αand VEGF in BALF in the emphysema group. Conclusion VEGF and TNF-αare related to the pathogenesis of emphysema of smoking rats, and may contribute to the development of emphysema in different pathways.

Citation： ZHANG Xiangyan,CHEN Ping,FENG Duanxing,YE Xianwei,LIU Weijia,HAN Jing.. Role of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Pathogenesis of Emphysema ZHANG Cheng*. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(4): 356-359. doi: Copy

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1. 王悦虹, 白春学, 洪群英, 等. 血管内皮细胞生长因子及其受体在大鼠肺气肿模型中的表达. 复旦学报( 医学版) , 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. 胡大为, 鲍春德, 陈顺乐, 等. 重组人Ⅱ 型肿瘤坏死因子受体-抗体融合蛋白治疗类风湿关节炎双盲随机多中心对照临床研究.中华风湿病学杂志, 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.

Chinese Journal of Respiratory and Critical Care Medicine

Role of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Pathogenesis of Emphysema ZHANG Cheng*

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