组胺对荷黑色素瘤C57BL-6小鼠微血管壁通透性的影响论文.docVIP

　　组胺对荷黑色素瘤C57BL/6小鼠微血管壁通透性的影响论文 秦迎松 庞训雷 于红丽 【摘要】 目的 研究组胺对荷黑色素瘤C57BL/6小鼠各器官及肿瘤微血管壁通透性的影响，为通过组胺增加抗体靶向药物在肿瘤局部的富集提供依据。方法 细胞悬液接种法制备荷瘤模型，伊文思蓝法检测各器官及肿瘤微血管壁通透性，组织化学方法观察组织结构改变。结果 ①成功建立荷瘤模型，成瘤率100％。②对照组伊文思蓝（Evans blue, EB）在各器官分布达平衡的过程不同：肝、肺存在明显再分配；小肠、脾和肿瘤组织中EB随时间不断积累，在高水平上保持平衡；心、肾中EB含量随时间的积累过程比较缓慢，升高幅度不显著；脑组织中EB含量极少。③组胺组分布达平衡前各组织中EB含量与对照组相应时间点相比变化较大，平衡后小肠、脾、肺(P 0.05)及肿瘤(P 0.01)组织中EB含量比对照组升高.freeline on the microvessel permeability in melanoma B16 burdened C57BL/6 mice to provide an experimental rationale for the use of histamine in the antibody-coupled anti-tumor therapy. Methods Cultured melanoma B16 cells pit of C57BL/6 mice (200 μl each). Model mice l/kg through the caudal vein, folloine 300 mg/kg hypo. The control group e points of 10 min, 30 min, 1 h, 2 h and 4 h after injection, the mice ine the optic density of EB in internal organs and tumor tissue eter at 620 nm. The structural changes ined using histochemical stain. Results ① The formation of melanoma model in mice ice: redistribution ulation of EB , spleen and tumor; sloulation of EB, in the heart and kidneys; feine changed the distribution pattern of EB in the test group, causing apparent plasma level fluctuation. After equilibration,.freel, spleen and lungs (P 0.05) and in the tumor (P 0.01), but not in the brain. ④ No apparent edema or hemorrhage could be seen in the internal organs in the histamine-treated model mice; but in the tumor，apparent microvessel congestion, increased plasma exudation, and bleeding or or under the pseudo-capsule ine increases the accumulation of EB in most tissues of the melanoma B16 burdened C57BL/6 mice, especially in the tumor tissue, causing no apparent injuries to the body, if histamine is not overloaded. Key ine; melanoma; vessel eability 肿瘤是危害人类健康的三大疾病之一。常规的术后放、化疗各有其局限性。近年来开发的肿瘤靶向给药系统,如抗体－药物偶联物等，因其具有定向在肿瘤局部富集、特异杀伤肿瘤细胞的优势，成为目前肿瘤治疗领域研究的热点。但是，血管壁的通透性却构成这些大分子药物进入瘤体的主要屏障。虽然许多实验证明肿瘤组织中微血管壁的通透性较正常组织微血管壁的通透性高，但抗体偶联物到达肿瘤组织的药量仍十分有限。据推算，肿瘤组织的单抗摄取量仅为0.005％（注入剂量/g）［1］。因此，血管壁的通透性构成了大分子载