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目的:通过建立慢性心理应激C57/B6小鼠荷瘤模型,观察应激反应对肿瘤生长、转移和血清血管内皮生长因子(VEGF)水平及肿瘤组织MVD、KDR和HIF-1α表达的影响。方法:C57/B6雄性小鼠40只分为A组(16只)、B组(16只)和C组(8只),A组移植肿瘤后每天行束缚应激;B组移植肿瘤后未行应激诱导;C组为正常对照。2周后检测肿瘤大小、质量、肺部和肝脏转移病灶数量,免疫组化(IHC)检测肿瘤新生血管局部CD31阳性细胞,计数微血管密度(MVD);ELISA法检测VEGF水平;蛋白质印迹法检测肿瘤组织局部VEGFR2(KDR)表达水平;RT-PCT检测缺氧诱导因子-1α(HIF-1α)转录水平。结果:A组荷瘤小鼠的肿瘤质量和体积与B组相比,差异有统计学意义,P<0.05;转移病灶数量上A、B组差异无统计学意义,P>0.05。A组肿瘤局部MVD与B组相比,差异有统计学意义,P<0.05;血清VEGF水平A组较B组、B组较C组均明显升高,差异均有统计学意义,P<0.01;A、B组肿瘤组织KDR表达水平及HIF-1α转录水平,差异均有统计学意义,P<0.05。结论:长期慢性心理应激能诱导肿瘤新生血管形成,促进肿瘤增长。
OBJECTIVE: To investigate the effect of stress on tumor growth, metastasis, serum VEGF and MVD, KDR and HIF-1α expression in C57 / B6 mice model of chronic psychological stress. Methods: 40 male C57 / B6 mice were divided into group A (16), group B (16) and group C (group 8). Group A received daily restraint stress after transplanted tumor; group B Line stress induction; C group as a normal control. Tumor size, mass, numbers of lung and liver metastases were detected after 2 weeks. Local CD31 positive cells were detected by immunohistochemistry (IHC), and microvessel density (MVD) was counted. VEGF level was detected by ELISA. Western blotting was used to detect tumor The local expression of VEGFR2 (KDR) was detected by RT-PCR. The transcription level of hypoxia-inducible factor-1α (HIF-1α) was detected by RT-PCR. Results: The tumor mass and volume of tumor-bearing mice in group A were significantly different from those in group B (P <0.05). There was no significant difference in the number of metastatic lesions between groups A and B (P> 0.05). Group A tumor local MVD compared with group B, the difference was statistically significant, P <0.05; serum VEGF levels A group than B group, B group were significantly higher than C group, the difference was statistically significant, P <0.01 There was significant difference in KDR expression level and HIF-1α transcription level between A and B groups (P <0.05). Conclusion: Long-term chronic psychological stress can induce tumor angiogenesis and promote tumor growth.