rmhTNF结合肝动脉化疗栓塞术治疗大鼠移植性肝癌的实验研究

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目的评价不同剂量重组改构人肿瘤坏死因子(recombinant mutant human tumor necrosis factor,rmhTNF)结合肝动脉化疗栓塞术(transarterial chemoembolization,TACE)治疗大鼠移植性肝癌的疗效及其机制。材料与方法将26只Wistar大鼠采用移植法建立Walker-256肝癌模型,于移植术后10天行MRI,测量肿瘤体积(V1),然后随机分成3组,分别行rmhTNF结合TACE治疗,14天后再行MRI以确定肿瘤体积(V2),计算各组肿瘤生长率(V2/V1),并用免疫组织化学法检测肿瘤Ⅷ因子及ki67表达情况。采用SPSS软件进行方差分析。结果 3组V2/V1分别为6.9813±1.0949、7.3911±0.7466、4.3200±0.7709,Ⅷ因子光密度平均值分别为0.2210±0.0163、0.2106±0.0121、0.1990±0.0155,ki67光密度平均值为0.3008±0.0366、0.2981±0.0433、0.2570±0.0252,差异均有统计学意义。与对照组比较,高剂量组对大鼠Walker-256移植性肝癌的生长率、血管生成、细胞增殖均有明显的抑制作用,低剂量组抑制作用不明显。结论不同剂量rmhTNF对肿瘤生长可能起不同作用。rmhTNF抑瘤作用部分通过抑制肿瘤血管生成及肿瘤细胞增殖实现。 Objective To evaluate the efficacy and mechanism of recombinant mutant human tumor necrosis factor (rmhTNF) combined with transarterial chemoembolization (TACE) in the treatment of transplanted liver cancer in rats. MATERIALS AND METHODS Twenty-six Wistar rats were implanted with Walker-256 hepatoma model. MRI was performed 10 days after transplantation. The tumor volume (V1) was measured and then randomly divided into 3 groups. The rats were treated with rmhTNF and TACE respectively. After 14 days MRI was performed to determine the tumor volume (V2). The tumor growth rate (V2 / V1) of each group was calculated and the expression of tumor factor Ⅷ and ki67 were detected by immunohistochemistry. ANOVA was performed using SPSS software. Results The V2 / V1 of the three groups were 6.9813 ± 1.0949, 7.3911 ± 0.7466 and 4.3200 ± 0.7709, respectively. The average optical density of the Ⅷ factor was 0.2210 ± 0.0163, 0.2106 ± 0.0121 and 0.1990 ± 0.0155, respectively. The average optical density of ki67 was 0.3008 ± 0.0366, 0.2981 ± 0.0433,0.2570 ± 0.0252, the differences were statistically significant. Compared with the control group, the high-dose group significantly inhibited the growth, angiogenesis and proliferation of Walker-256 hepatocellular carcinoma in rats, while the inhibition in low-dose group was not obvious. Conclusion Different doses of rmhTNF may play different roles in tumor growth. The antitumor effect of rmhTNF is partly achieved by inhibiting tumor angiogenesis and tumor cell proliferation.
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