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目的探讨雷帕霉素对人肝癌裸鼠皮下移植瘤生长的影响及可能机制。方法建立人肝癌裸鼠皮下移植瘤模型,随机分组后给予雷帕霉素常规剂量(1.5mg/kg.d-1)、低剂量(0.15mg/kg.d-1)、高剂量(4.5mg/kg.d-1)腹腔注射,对照组给予相同体积生理盐水。用药21d后处死动物,称量鼠重、瘤重,计算抑瘤率;CD34标记血管内皮细胞后行肿瘤微血管密度(MVD)计数;ELISA法检测血清中血管内皮细胞生长因子(VEGF)表达水平。结果与对照组比较,常规剂量雷帕霉素明显抑制了肿瘤生长,并降低了肿瘤MVD及血清VEGF水平(P<0.05),低剂量、高剂量组皮下移植瘤、MVD、VEGF水平均受到一定程度抑制,但是无统计学意义(P>0.05),实验中还发现高剂量组裸鼠体重明显下降(P<0.05)。结论常规剂量雷帕霉素可抑制肿瘤血管生成,从而抑制肿瘤生长,这为肝癌肝移植术后免疫抑制剂选择提供实验依据。
Objective To investigate the effect of rapamycin on the growth of human hepatocellular carcinoma xenograft in nude mice and its possible mechanism. Methods A subcutaneous xenograft tumor model of human hepatocellular carcinoma was established in nude mice. The mice were randomly divided into 5 groups: normal dose of rapamycin (1.5mg / kg.d-1), low dose of 0.15mg / kg.d-1, / kg.d-1) intraperitoneal injection, the control group was given the same volume of saline. The rats were sacrificed 21d after treatment, weight and weight of the mice were weighed, and the tumor inhibition rate was calculated. The number of tumor microvessel density (MVD) was counted after labeling of vascular endothelial cells with CD34, and the expression of VEGF in serum was detected by ELISA. Results Compared with the control group, the conventional dose of rapamycin significantly inhibited tumor growth and reduced the tumor MVD and serum VEGF levels (P <0.05). The subcutaneous xenografts, MVD and VEGF levels in both low and high dose groups were all decreased But there was no statistical significance (P> 0.05). The body weight of nude mice in high dose group was significantly decreased (P <0.05). Conclusion Conventional doses of rapamycin can inhibit tumor angiogenesis, thereby inhibiting tumor growth, which provides an experimental basis for the selection of immunosuppressive agents for liver cancer after liver transplantation.