壁虎醇提物对H22肝癌血管新生的抑制作用  

Inhibition effects of Gekko ethanol extract on the angiogenesis of H22 hepatoma

作　　者：郭梦丽 王建刚[1] 靳颖[1] 

机构地区：[1]河南科技大学医学院药理学与分子生物学实验室,河南洛阳471000

出　　处：《中国临床药理学杂志》2016年第24期2282-2285,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河南省科技重点攻关基金资助项目(102102310063)

摘　　要：目的研究壁虎醇提物(GEE)对H22小鼠肿瘤组织血管新生的抑制作用及其机制。方法建立腋下移植H22肝癌模型,按照体重随机分为5组:模型组(0.9%Na Cl)、对照组(2 mg·kg^(-1)阿霉素)和高、中、低3个剂量实验组(GEE:80,40,20 mg·kg^(-1)),连续腹腔注射10 d,计算抑瘤率;用免疫组化法观察血管内皮细胞标记物(CD34)表达水平,计算新生微血管密度(MVD);以免疫印迹法检测血管内皮生长因子A(VEGF-A)、基质金属蛋白酶(MMP-2)、细胞外信号调节激酶(ERK)、磷酸化的细胞外信号调节激酶(P-ERK)的表达。结果高、中、低3个剂量实验组的抑瘤率分别为63.18%,50.91%,44.68%,说明GEE对H22小鼠移植瘤的抑瘤作用较明显。模型组小鼠肿瘤组织MVD为平均每个视野(24.7±4.1)个,与模型组比较,对照组、高、中、低3个剂量实验组的MVD分别为平均每个视野(13.6±3.6),(8.0±1.6),(11.0±1.1),(13.9±1.7)个,其中3个剂量实验组差异有统计学意义(均P<0.01)。模型组、对照组、低中高3个剂量实验组的VEGF-A与β-actin灰度比值平均分别为0.17,0.10,0.01,0.03,0.04;这5组的MMP-2与β-actin灰度比值平均分别为1.68,1.27,0.48,1.15,1.50,而P-ERK与ERK灰度比值平均分别为0.10,0.07,0.06,0.07,0.08,与模型组相比,这4组差异均有统计学意义(均P<0.01),说明GEE组和对照组的VEGF-A、MMP-2、P-ERK蛋白水平均明显减弱。结论 GEE可抑制小鼠H22肝癌移植瘤的生长,其抗肿瘤作用机制可能与降低肿瘤组织血管生成相关因子VEGF-A、MMP-2、P-ERK的表达及降低微血管密度有关。Objective To investigate the inhibitory effect of Gekko etha- nol extract （GEE） on angiogenesis of H22 hepatoma and discuss its po- ssible molecular mechanism. Methods The H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor - as follow ： model bearing group 2 mg - kg-1）, and high, mice were randomly divided into five groups （ sailing ）, control group （ adriamycin, middle and low dosages experimental groups （GEE：80, 40, 20 mg - kg--） ,ten mice in each group. For 10 days of continuous intraperitoneal injection, the tumor inhibition rate was calcu- lated. The levels of a vascular endothelial cell marker （CD34） were de- tected by immunohistochemical. The microvessel density （MVD） was calculated. The expressions of vascular endothelial growth factor - A （ VEGF - A ）, matrix metalloproteinase - 2 （ MMP - 2 ）, extracelluar signal regulated kinase （ERK）, regulating kinase phosphorylation of extracellular signals（ P - ERK） were detected by Western blot. Results GEE were found to markedly inhibit the H22 mice - transplanted tumor growth. The inhibitory rate of high, middle and low dosages experimental groups were 63.18%, 50. 91% and 44.68%, respectively. For each view of model group and control group, mice tumor MVD were （24.7±4. 1 ）, （13.6 ±3.6） count. Compared with model group, high, middle, low experimental groups mice tumor MVD decreased significantly（P 〈0. 01 ）, for each view were （8.0 ± 1.6）, （ 11.0 ± 1.1 ）, （ 13.9 ± 1.7） count, respectively. Model group, control group and low, middle, high experimental groups of VEGF - A and beta actin grayscale average ratio were 0. 17,0. 10,0. 01,0. 03,0. 04. The five groups of MMP - 2 and beta actin grayscale average ratio were 1.68,1.27,0. 48,1.15,1.50. The five groups of P- ERK and ERK grayscale average ratio were 0. 10,0.07,0. 06,0. 07,0. 08. Compared to the model group, control group and three dosages experimental groups decreased significantly�

关 键 词：壁虎醇提物 H22肝癌 ERK信号转导通路 血管生成 

分 类 号：R28[医药卫生—中药学]