蛇床子素对大鼠肝癌动物模型肝细胞生物行为学特性及血管特征的影响

Effect of osthole on the bio-behavioral characteristics and vascular characteristics in hepatocellular carcinoma model rat

目的探讨蛇床子素对二乙基亚硝胺致癌和Walker-256移植瘤Wistar大鼠的生物行为学特性及血管特征的影响。方法选取造模成功的二乙基亚硝胺致癌和Walker-256移植瘤的Wistar大鼠各20只,前者均分为A组和C组,后者均分为B组和D组,A、B2组给予等体积的生理盐水灌胃,为对照组;C、D2组给予2.5μg/(g·d)蛇床子素灌胃,为治疗组。治疗4周后,对各组进行微血管直径的测量,肿瘤微血管密度的计数,肿瘤直径的测量,肿瘤分化程度评价以及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达。结果治疗4周后,C组肿瘤直径较A组明显降低(P<0.01),D组肿瘤直径较B组有一定程度的降低(P<0.05);C组较A组,D组较B组大鼠的门脉癌栓率均显著性降低(P<0.01);2治疗组肿瘤细胞分化程度有一定程度的升高,但与对照组比较差异无统计学意义;微血管密度和微血管直径C组较A组,D组较B组均有一定程度的降低(P<0.05)。C组较A组,D组较B组肿瘤瘤块体积均明显降低(P<0.01)。A、B组血管内皮细胞VEGF呈现高表达状态,C、D组经过蛇床子素4周治疗后,血管内皮细胞VEGF的表达均明显降低。结论蛇床子素可通过影响肝细胞癌生物行为学特性及血管特征而抑制2种肝癌实验动物模型肝癌的生长。

Objective To investigate the effect of osthole on the bio-behavioral characteristics and vascular characteristics in N-nitrosodiethylamine and Walker-256 transplantable tumor Wistar rats. Methods 20 rats with N-nitrosodiethylamine-induced tumor were divided into A,C group,another 20 rats with Walker-256 transplantable tumor Wistar rats were divided into B,D groups,each had 10 rats. Rats in group A and C were given certain saline as control groups,and rats in group B and D were given 2. 5 μg /( g·d) osthole gavage treatment. After 4 weeks treatment,capillary diameter,tumor microvessel density,tumor diameter,tumor differentiation of each group were measured and the expression of vascular endothelial growth factor( VEGF)in each group were measured by immunohistochemistry assay. Results After 4 weeks osthole treatment,tumor diameter of group C was significantly lower than that of group A( P < 0. 01),and group D was significantly lower than that of group B( P < 0. 05). Ratio of portal thrombosis in group C and D were significantly lower than that of group A and group B,respectively( P < 0. 01). The degree of tumor cell differentiation were increased in group C and D,and there were no significant difference with two control group. Microvascular density and microvascular diameter in group C and D were significant lower than that in group A and B,respectively( P < 0. 05). Tumor volumes in treatment groups( C and D) were significantly lower than that in control groups( A and B,P < 0.01). VEGF showed high expression in group A and B,and decreased in groups C and D after 4 weeks osthole treatment. Conclusion Osthole could inhibit hepatocellular carcinoma growth in two experimental animal models by influencing the bio-behavioral characteristics of hepatocellular carcinoma and vascular characteristics.