Abstract
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。
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