目的研究内皮-单核细胞激活多肽(EMAP—Ⅱ)对脑胶质瘤大鼠血肿瘤屏障(BTB)通透性的影响以及最佳的作用条件。方法应用免疫组织化学方法观察内源性EMAP—Ⅱ在正常脑组织和脑胶质瘤组织中的分布;采用伊文氏兰(EB)法检测不同浓度外源性EMAP—Ⅱ作用后血肿瘤屏障通透性的变化。结果在正常脑组织,内源性EMAP—Ⅱ主要表达在脑微血管和神经元;在脑肿瘤组织,主要表达在肿瘤组织微血管和肿瘤细胞。不同浓度的外源性EMAP—Ⅱ可使血肿瘤屏障对伊文氏兰的通透性增加,对正常脑组织的通透性没有影响,在EMAP—Ⅱ的作用1h时达到高峰,以后逐渐下降,12h时基本恢复至灌注前水平;40ng/kg体重的浓度为EMAP—Ⅱ的的最适作用浓度。结论EMAP—Ⅱ能够以剂量依赖的方式选择性增加血肿瘤屏障的通透性。
Objective To investigate the effect of endothelial-monocyte activating polypeptide Ⅱ (EMAP-Ⅱ) on the permeability of blood-tumor barrier (BTB) in brain glioma rats and determine the optimal condition of EMAP-Ⅱ. Methods Immunohistochemistry was used to measure the distribution of endogenous EMAP-Ⅱ in the normal brain tissues and the tumor tissues. The permeability of BTB after different concentration of exogenous EMAP-Ⅱ infusion was measured by Evans blue (EB) assay. Results In glioma rats' model, immunohistochemistry analysis showed that endogenous EMAP- Ⅱ mainly expressed in the microvessels and neuron in normal brain tissues, while in tumor microvessels and tumor cells in tumor tissues. The effect of different concentration of exogenous EMAP-Ⅱ on BTB permeability for EB extravasation increased, but no normal brain was involved. The permeability of BTB reached a peak at 1 h after administration of exogenous EMAP-Ⅱ, then decreased gradually and restored to the level before administration of exogenous EMAP-Ⅱ. 40 ng/kg tissues is the optimal concentration of exogenous EMAP-Ⅱ. Conclusion EMAP-Ⅱ could increase the permeability of BTB selectively in a dose-dependent manner.