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目的探讨祁州漏芦提取物(Rhaponticum uniflorum extract,RUE)对小鼠H_(22)移植瘤血管生成及细胞凋亡的影响。方法建立H_(22)肝癌皮下移植瘤小鼠模型,随机分为模型组、祁州漏芦提取物高、中、低剂量组和氟尿嘧啶组。连续干预10 d。采用苏木素-伊红(HE)染色法观察肿瘤组织病理学变化,采用DNA ladder法检测肿瘤细胞凋亡情况,采用免疫组织化学法检测肿瘤组织内微血管密度(microvessel density,MVD),采用免疫印迹法检测肿瘤组织血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)和缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)的蛋白表达。结果与模型组比较,祁州漏芦提取物组肿瘤细胞生长受抑,坏死程度较严重;DNA梯形条带显著增多;肿瘤组织微血管密度显著降低;血管内皮生长因子、血管内皮生长因子受体2和缺氧诱导因子-1α蛋白的表达均显著降低。结论祁州漏芦提取物对H_(22)移植瘤小鼠具有抑制血管生成和诱导细胞凋亡作用,其抗血管生成作用可能与下调移植瘤组织血管内皮生长因子、缺氧诱导因子-1α、血管内皮生长因子受体2的蛋白表达有关。
Objective To investigate the effects of Rhaponticum uniflorum extract (RUE) on angiogenesis and apoptosis of H22 tumors in mice. Methods The mouse model of H22 hepatoma subcutaneous transplantation tumor was established and randomly divided into model group, high, medium and low dose Qilu Gum extract and fluorouracil group. Continuous intervention for 10 days. The hematoxylin and eosin (HE) staining was used to observe the histopathological changes of tumor cells. The apoptosis of tumor cells was detected by DNA ladder method. The microvessel density (MVD) in tumor tissues was detected by immunohistochemical method. The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2) and hypoxia inducible factor-1α (HIF- 1α) protein expression. Results Compared with the model group, the growth of tumor cells was inhibited and the degree of necrosis was more serious. The DNA ladder band was significantly increased. The density of tumor microvessel was significantly decreased. The expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2 And hypoxia inducible factor-1α protein expression were significantly reduced. Conclusion The extract of Qilu Gumluo can inhibit angiogenesis and induce apoptosis in H22 tumor - bearing mice, and its antiangiogenic effect may be related to the down - regulation of the expression of vascular endothelial growth factor, hypoxia - inducible factor - 1α, Vascular endothelial growth factor receptor 2 protein expression.