海兔素对小鼠H_(22)移植瘤侵袭及免疫调节影响  

Effect of aplysin on invasion and immunomodulatory of hepatocarcinoma 22 in mice

作　　者：王青[1] 梁惠[1] 刘颖[2] 戈娜[1] 马爱国[1] 

机构地区：[1]青岛大学医学院医学营养研究所,山东青岛266021 [2]青岛大学医学院细胞与分子生物学实验室

出　　处：《中国公共卫生》2014年第10期1265-1267,共3页Chinese Journal of Public Health

基　　金：山东省科技发展计划(2012YD15011);国家"十二五"科技支撑计划(2012BAD33B01)

摘　　要：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 investigate the effect of aplysin on tumor invasion and immunomodulation in mice with hepatocarcinoma-22（H22） implantation.Methods Forty Kunming mice were randomly divided into four groups：model group and aplysin treatment groups（25,50,100 mg /kg-1/d-1） and H22 cells were inoculated subcutaneously into left anteromedial of the mice of all the groups.Except for the model group,all the mice in the other 3 groups were treated with aplysin of different dosage by gavage on the second day and sacrificed after 15 days.We weighed the tumor tissue and calculated the tumor inhibition rate.The expressions of matrix metalloproteinases-9（MMP-9）,vascular endothelial growth factor（VEGF）,and proliferating cell nuclear antigen（PCNA） in tumor tissue were determined simultaneously with immunohistochemistry.And the levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in serum were measured with enzyme-linked immunosorbent assay（ELISA）.Results Aplysin decreased the tumor weight significantly in a dosedependent manner,with the tumor inhibition rates of 28.31%,33.84%,and 42.96%,respectively.For the mice with aplysin treatment at the concentrations of 50 and 100 mg /kg-1/d-1,the expressions of MMP-9 were 54.29 ±6.41% and29.31 ± 3.15%,and were significantly different from that of model group（74.80 ± 8.06%）.The expressions of VEGF and PCNA were obviously inhibited in a dose-effect mamer（P 〈0.05）.In moderate and high-dose asplysin treatment groups,the level of IL-6 in serum were 0.34 ± 0.050 and 0.37 ± 0.04 and the TNF-α were 1.26 ± 0.21 and 1.49 ± 0.17,which were significantly higher than those of model group（P 〈0.05）.Conclusion Aplysin could inhibit tumor growth by suppressing extracellular matrix degradation and angiogenesis and improving the immune capacity in mice.

关 键 词：海兔素 H22肿瘤 基质金属蛋白酶-9(MMP-9) 血管内皮生长因子(VEGF) 增殖细胞核抗原(PCNA) 白细胞介素-6(IL-6) 肿瘤坏死因子-α(TNF-α). 

分 类 号：R181.24[医药卫生—流行病学]