骨内单次注射辛伐他汀促进小鼠乳腺癌肿瘤血管正常化的研究

摘要

目的 研究骨内单次注射辛伐他汀对小鼠乳腺癌肿瘤血管结构和功能的影响.方法 构建小鼠乳腺癌原位模型,分别给予骨内单次注射辛伐他汀(50μg)或空白载体.α-SMA/CD31免疫荧光双染观察肿瘤血管的周细胞/血管内皮细胞覆盖率;尾静脉注射伊文氏蓝染料观察肿瘤血管渗透性;免疫组化检测肿瘤内部HIF-1α表达水平的变化.结果 免疫荧光双染发现与对照组相比辛伐他汀组肿瘤血管周细胞覆盖增多(P<0.05);肿瘤组织内伊文氏蓝含量显著降低(P<0.05),提示肿瘤血管渗透性减低,肿瘤血管趋于成熟;免疫组化显示肿瘤内部HIF-1α的表达水平降低,乳腺癌肿瘤组织缺氧改善.结论 骨内单次注射辛伐他汀能够提高新生血管的周细胞覆盖,促进乳腺癌肿瘤血管正常化.%Objective To investigate the effect of single dose intraosseous injection of simvastatin on tumor vascular structure and function in murine breast cancer. Methods BALB/c mice and 4T1 murine breast cancer cells were used to establish a subcutaneous xenograft model. The mouse model of orthotopic breast cancer received intraosseous injection of a single dose of simvastatin (50 μg) or vehicle only. Frozen tumor tissue sections were prepared for co-immunostained with CD31 andα-SMA. Evans blue dye was injected into the tail vein to observe the vascular permeability. The expression level of HIF-1αwas detected by immunohistochemistry. Results Immunofluorescence dual staining showed that intraosseous injection of simvastatin increased the number of perivascular pericytes in the tumor vessel(P < 0. 05), Evans blue dye content showed that in vivo vessel permeability in the tumor tissue was significantly decreased(P < 0. 05), and the immunohistochemistry results showed that local hypoxic area was significantly improved. Conclusions Single dose intraosseous injection of simvastatin can promote the normalization of tumor vasculature by improving the coverage of pericytes.