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目的观察海兔素对H22荷瘤小鼠肿瘤生长侵袭的影响及免疫调节作用。方法昆明小鼠40只,随机分为模型组、海兔素低、中、高剂量组(n=10)。各组小鼠左前腋下皮下接种H22肝癌细胞,建立小鼠H22移植性肿瘤模型,次日除模型组外,海兔素低、中、高剂量组分别以25、50、100 mg/kg海兔素灌胃,于15 d后处死,剥离肿瘤,称重,计算抑瘤率;采用免疫组化法测定肿瘤组织中基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)及增殖细胞核抗原(PCNA)表达,酶联免疫吸附试验测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。结果低、中、高剂量海兔素组小鼠抑瘤率分别为28.31%、33.84%、42.96%,呈量效依赖性;经50、100 mg/kg海兔素处理后,小鼠肿瘤组织中MMP-9表达阳性率分别为(54.29±6.41)%、(29.31±3.15)%,明显低于模型组(74.80±8.06)%;VEGF和PCNA阳性表达逐渐下降,呈剂量效应关系(P<0.05);中、高剂量海兔素组小鼠血清中IL-6和TNF-α水平[分别为(0.34±0.050)、(0.37±0.04)和(1.26±0.21)、(1.49±0.17)μg/L],均明显高于模型组,差异有统计学意义(P<0.05)。结论海兔素可抑制H22小鼠肿瘤增长,其机制可能与海兔素抑制肿瘤组织细胞外基质降解以及新生血管形成,同时提高机体免疫能力有关。
Objective To observe the effect of sea rabbit on tumor growth and invasion of H22 tumor-bearing mice and its immunoregulatory effects. Methods Forty Kunming mice were randomly divided into model group and sea-rabbit low, medium and high dose group (n = 10). H22 hepatoma cells were inoculated subcutaneously in the left armpit of the mice in each group to establish a mouse H22 transplanted tumor model. The rats in the low, medium and high dose groups were treated with 25, 50, 100 mg / kg sea Rabbit was intragastrically administrated and killed after 15 days. The tumor was dissected and weighed to calculate the tumor inhibition rate. The expressions of MMP-9, VEGF and VEGF were detected by immunohistochemistry The expression of PCNA and IL-6 and TNF-α in serum were measured by enzyme linked immunosorbent assay (ELISA). Results The tumor inhibition rates of mice in low, middle and high dose sea-rabbit groups were 28.31%, 33.84% and 42.96%, respectively. In the dose-dependent manner, the mice tumor tissues (54.29 ± 6.41)%, (29.31 ± 3.15)%, respectively, which was significantly lower than that of model group (74.80 ± 8.06)%. The positive expression of VEGF and PCNA decreased gradually with a dose-response relationship (P < 0.05). The levels of IL-6 and TNF-α in serum of middle and high dose sea-untreated mice were (0.34 ± 0.050), (0.37 ± 0.04) and (1.26 ± 0.21), (1.49 ± 0.17) μg / L], were significantly higher than the model group, the difference was statistically significant (P <0.05). Conclusions Hyposptorin can inhibit tumor growth in H22 mice, and its mechanism may be related to the decrease of extracellular matrix degradation and neovascularization in the tumor tissue and the enhancement of immune function.