血管形成的测定方法

来源:岁月联盟 作者: 时间:2015-05-10

  2.5 肿瘤模型

  肿瘤模型是用来检测药物抗血管生成和抗肿瘤作用的最终模型, 包括人肿瘤模型及动物肿瘤模型。小鼠Lewis 肺癌和黑色素B16 等高转移模型是常用的动物肿瘤模型, 人肿瘤模型最常用的是裸鼠异种移植瘤[25]。利用高转移的裸鼠移植瘤还可同时观察抗血管生成物质的抗肿瘤转移能力。肿瘤生长超过一定的大小就需要形成新的血管来获得氧气、营养和排除代谢废物,因此一些特殊组织学分析,如血管密度、血流、凝血作用、肿瘤细胞的凋亡或坏死等都可用来作为检测物质对新生血管形成影响作用的指标。

  与CAM模型相比,肿瘤模型更适合研究肿瘤血管的发生。待测药物的吸收、分配状态、药效等在肿瘤模型上都能得到比较精确的结果。另外,肿瘤模型也可用来检测新药物是否具有抗新生血管形成或抗血管生长的作用。然而,实验所用的肿瘤细胞,特别是经皮下移植的肿瘤细胞与常位生长的肿瘤细胞的生长环境是不同的,这可能会影响实验结果。此外,要检测新血管的形成,最后需要处死实验动物,并需要花费长时间来准备组织分析,这就不可能进行实时非侵袭性的研究[26]。

  3 结 语

  随着目前一系列潜在的血管形成抑制剂在癌症临床第2、3阶段的实验成功,开发新的抗血管药物已经成为治疗癌症和其他一些疾病的趋势,而在临床前的研究中,必须找到更为有效、合适的方式来检测癌症抑制剂对癌细胞或血管的抑制效果。同时,对于一系列的体内、体外测定法,必须认识到它们的局限性,才能对结果作出相应的精确的解释。

  体外测定法的实施是测定待测试物质作用关键性的第一步,给我们提供了大量有用的信息。然而,体外与体内环境之间存在着很大的差异,并不能完全反映体内血管的发生。因此,要对一种物质在血管形成过程中的作用有充分的理解和评价,必须使用一种以上的体外测定方法来研究待测物质在血管发生中的作用,然后使用一种以上的体内测定法来验证在体外测定法中所观察到的结果。

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