目的研究内皮-单核细胞激活多肽II(endothelial monocyte activating polypeptide-II,EMAP-II)选择性开放血肿瘤屏障(blood-tumor barrier,BTB)的作用机制。方法荷瘤大鼠被随机分成4组(每组12只):对照组,EMAP-II组,寡霉素组和寡霉素+EMAP-II组。采用伊文思蓝(Evans blue,EB)渗透性实验评估各组BTB通透性变化情况;Western Blot法检测脑微血管内皮细胞上紧密连接相关蛋白ZO-1的表达水平变化;双重免疫荧光法检测EMAP-II和α-ATP合成酶在脑微血管内皮细胞上的分布。结果 EMAP-II组BTB通透性显著高于对照组和寡霉素组(<0.01),紧密连接相关蛋白ZO-1的表达水平显著降低(<0.01),其作用受到ATP合成酶抑制剂寡霉素(Oligomycin)的显著抑制(<0.05);EMAP-II与α-ATP合成酶在胶质瘤微血管内皮细胞上共定位。结论 EMAP-II可能通过开放紧密连接增强BTB的通透性,脑微血管内皮细胞上的α-ATP合成酶是其可能的作用位点。 Objective To investigate the mechanism of selective opening of blood-tumor barrier (BTB) by endothelial monocyte activating polypeptide-II (EMAP-II). Methods Tumor-bearing rats were randomly divided into 4 groups (12 in each group): control group, EMAP-II group, oligomycin group and oligomycin + EMAP-II group. The changes of permeability of BTB in each group were evaluated by Evans blue (EB) permeability test. The expression of tight junction-related protein ZO-1 in brain microvascular endothelial cells was detected by Western Blot. The levels of EMAP -II and α-ATP synthase on brain microvascular endothelial cells. Results The BTB permeability of EMAP-II group was significantly higher than that of control group and oligomycin group (P <0.01). The expression of tight junction-associated protein ZO-1 was significantly decreased (<0.01), and its effect was inhibited by ATP synthase inhibitor (P <0.05). EMAP-II co-localized with α-ATP synthase on glioma microvascular endothelial cells. Conclusion EMAP-II may enhance the permeability of BTB through open tight junctions, and α-ATP synthase on brain microvascular endothelial cells may be its possible site of action.