血管内皮细胞生长因子和肿瘤坏死因子α在大鼠肺气肿中的作用

目的探讨血管内皮细胞生长因子(VEGF)和肿瘤坏死因子α(TNF-α)在大鼠肺气肿中的作用。方法 48只大鼠随机分为正常对照组、肺气肿组、rhTNFR:Fc干预组和假干预组。肺气肿组、干预组和假干预组予以香烟熏吸。烟雾暴露达1个月时,干预组予以TNF-α拮抗剂重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)皮下注射,假干预组给予空白对照制剂。熏烟80d后处死大鼠。大鼠肺组织切片行HE染色观察形态学改变。ELISA法测定血清、BALF中TNF-α浓度及BALF中VEGF浓度。结果与正常对照组比较,肺气肿组肺平均内衬间隔(MLI)升高,平均肺泡数(MAN)降低,BALF中VEGF水平降低,血清、BALF中TNF-α浓度升高,差异均有统计学意义(P0.05)。与肺气肿组比较,rhTNFR:Fc干预组MLI无显著差异(P0.05),MAN增高(P0.05);BALF中TNF-α、VEGF浓度无显著差异(P0.05),血清中TNF-α浓度降低(P0.05)。肺气肿组BALF中VEGF水平与TNF-α浓度无相关性(P0.05)。结论 VEGF表达降低和TNF-α表达增加与吸烟大鼠的肺气肿形成有关。VEGF与TNF-α可能各自独立促进肺气肿的发生发展。

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

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 sham intervention 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-α in serum and 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-α in serum and BALF were higher,and the level of VEGF in BALF was lower significantly （P0.05）.After the intervention with rhTNFR：Fc,MAN increased and the serum TNF-α decreased significantly compared with the emphysema group （P0.05）.However there were no significant differences in MLI,VEGF,and TNF-α in BALF （P0.05）.No correlation was found between the level of TNF-α and VEGF in BALF in the emphysema group.Conclusion VEGF and TNF-α are related to the pathogenesis of emphysema of smoking rats,and may contribute to the development of emphysema in different pathways.