胸腔内注射重组人血管内皮抑素对裸鼠恶性胸腔积液的治疗作用  

Therapeutical Effects of Pleural Injecting Recombinant Human Endostain to Malignant Pleural Effusion Nude Mice Model

作　　者：周明[1] 李敏[1] 杨华平[1] 胡成平[1] 

机构地区：[1]中南大学湘雅医院呼吸科,长沙410008

出　　处：《中国肺癌杂志》2015年第5期266-271,共6页Chinese Journal of Lung Cancer

基　　金：十二五国家科技支撑计划课题(No.2013BI09B09)资助~~

摘　　要：背景与目的恶性胸腔积液(malignant pleural effusion,MPE)临床预后不佳,胸腔内抗血管治疗可能对恶性胸腔积液具有治疗作用,本研究旨在探讨胸腔内注射重组人血管内皮抑素、顺铂、重组人血管内皮抑素联合顺铂对裸鼠恶性胸腔积液的治疗作用。方法 BALB/c裸鼠胸膜腔内注射Lewis肺癌细胞(Lewis lung cancer cell,LCC)构建恶性胸腔积液模型,造模后分别胸腔内注射重组人血管内皮抑素(E)、顺铂(P)以及重组人血管内皮抑素联合顺铂(EP)并分析各组裸鼠胸腔积液量、胸膜肿瘤微血管密度(micro vessel density,MVD)以及血管生成、凋亡相关基因的表达变化。结果重组人血管内皮抑素及重组人血管内皮抑素联合顺铂胸腔内注射可以使裸鼠MPE量减少,且与裸鼠胸腔肿瘤组织MVD下降呈正相关;且重组人血管内皮抑素及重组人血管内皮抑素联合顺铂胸腔内注射后,MPE裸鼠胸腔肿瘤组织血管内皮生长因子(Vescular epidermal growth factor-α,VEGF-α)表达下降、低氧诱导因子-α(hypoxia induced factor-1,HIF1-α)表达升高。结论胸腔内注射LLC细胞可成功制作裸鼠MPE模型。重组人血管内皮抑素裸鼠胸膜腔内注射对MPE裸鼠具有治疗作用,其治疗作用可能是通过下调VEGF-α,抑制肿瘤新生血管生成,下调微血管密度而达成的。Background and objective hTe prognosis of malignant pleural effusion （MPE） was poor, injecting anti-angiogenesis agents in pleural cavity might be to reducing the volume of pleural effusion. hTe aim of this study is to investigate the therapeutical effect of pleural injection of recombinant human endostain, cisplatin and recombinant human endostain combined with cisplatin to MPE nude mice. Methods MPE model was built by intrpleural injection of Lewis lung cancer cells （LCC） into BALB/c nude mice. Intrpleural injection of recombinant human endostain （E）, cisplatin （P） and recombinant hu-man endostain combined with cisplatin （EP） was performed, MPE volume was measured, immunohistochemistry of CD31 was carried out to calculate micro vessel density （MVD）, angiogenesis and apoptosis gene expression was detected. Results MPE volume was reduced by intrapleiral injection of recombinant human endostain and recombinant human endostain com-bined with cisplatin, MPE volume was positive correlated with MVD. Vescular epidermal growth factor-α（VEGF-α） expression reduced simultaneously with expression of hypoxia induced factor-1 （HIF1-α） elevated at the same time. Conclusion MPE model could be made by intrapleural injection of LLC. Intrapleural injection of recombinant human endostain could reduce MPE volume of nude mice. hTe potential molecular mechanism of the therapeutical effects of intapleural injection of recombi-ant endostatin might be related to the downregulation of VEGF-αexpression and neovascularization.

关 键 词：肺肿瘤 胸腔积液 重组人血管内皮抑素 

分 类 号：R734.2[医药卫生—肿瘤]