目的 选择性环氧化酶-2（cyclooxtgenase-2，COX-2）抑制剂尼美舒利（Nimesulide,NIM）联合顺铂(Cisplatin，CDDP)对于肺癌A549裸鼠动物模型中肿瘤新生血管的影响。方法 （1）培养肺癌A549细胞，构建肺癌A549裸鼠移植瘤模型。（2）药物干预，对照组，尼美舒利组，顺铂组，尼美舒利与顺铂联合组，依据随机数字表法将研究 对象分为4组每组8只，观察一般状态。（3）用免疫组化检测肺癌A549裸鼠移植瘤内新生血管因子， 血管转换生长因子TGF-β、环氧化酶COX-2、碱性成纤维细胞生长因子bFGF，以明确尼美舒利单独或者联合顺铂对肺癌A549裸鼠移植瘤新生血管的影响及其机制。 结果（1）成功构建肺癌A549裸鼠移植瘤模型，裸鼠背部皮下形成圆形、椭圆形、不规则形结节，，无裸鼠建模死亡。（2）NIM+DDP组对肿瘤的抑制最强，抑瘤率最大，（P＜0.001），有明显差异，有统计学意义。（3）NIM+DDP组的bFGF、TGF-β1的阳性表达最弱，NIM+DDP组和DDP组的阳性表达比较，（P＜0.001），有统计学意义。（4）COX-2阳性表达呈对照组＞NIM组＞DDP组＞NIM+DDP组。结论（1）选择性COX-2抑制剂联合顺铂对肺肿瘤的生长有抑制作用，抑瘤率明显高于顺铂单药组。（2）选择性COX-2抑制剂联合顺铂对新生血管因子bFGF、TGF-β1、COX-2表达的抑制效果更显著，对肺癌A549细胞裸鼠移植瘤的生长的抑制更显著。

Abstract Objective Effect of selective cyclooxtgenase-2 (cox-2) inhibitor Nimesulide (NIM) combined with Cisplatin (CDDP) on tumor neovascularization in A549 nude mouse model of lung cancer. Methods (1) cultured A549 cells and established A549 lung xenografts in nude mice model. (2) intervention, control group, nimesulide group , cisplatin group, nimesulide + cisplatin group, n= 8, to observe the clinical signs. (3) To specify the effect and mechanism of nimesulide alone or in combination with cisplatin on A549 lung cancer xenograft tumor angiogenesis, we detected A549 lung cancer xenograft tumor angiogenesis factor, vascular transforming growth factor (TGF-β1), cyclooxygenase(COX-2),and basic fibroblast growth factor (bFGF) in immunohistochemistry. Results (1) We constructed A549 lung cancer xenografts in nude mice successfully , formed a round, oval, irregular-shaped nodules subcutaneously. (2) NIM could inhibit the growth of A549 lung cancer cells in nude mice. (3) NIM + DDP group and the positive expression of DDP group have significant differences (P ＜0.001).(4) Cox-2 positive expression in the control group ＞NIM group DDP group ＞ NIM + DDP group. Conclusion (1) Selective cox-2 inhibitors combined with cisplatin can inhibit the growth of lung tumors, and the inhibitory rate is significantly higher than that of single drug. (2) The selective COX-2 inhibitors in combination with cisplatin showed more significant inhibitory effect on the angiogenesis and A549 cell xenografts tumor in nude mice.