天然产物研究与开发 ›› 2016, Vol. 28 ›› Issue (6): 943-948.doi: 10.16333/j.1001-6880.2016.6.022

• 开发研究 • 上一篇    下一篇

大蒜素对大鼠实验性大肠癌的作用及其机制研究

王先坤1,王雪2*,黄建3   

  1. 1 黔南布依族苗族自治州中医医院;2 黔南布依族苗族自治州人民医院,都匀 558000;3 浙江大学附属第二医院胃肠外科,杭州 310009
  • 出版日期:2016-06-30 发布日期:2017-01-17

Effects of Allicin on Experimental Colorectal Cancer in Rats and its Mechanism

WANG Xian-kun1,WANG Xue 2*, HUANG Jian3   

  1. 1 Qiannan Buyi and Miao Autonomous Prefecture,Chinese Medicine Hospital,Duyun 558000,China;  2 Qiannan Buyi and Miao Autonomous Prefecture People's Hospital,Duyun 558000,China; 3 Second Affiliated Hospital of Zhejiang University of Gastrointestinal Surgery,Hangzhou 310009,China
  • Online:2016-06-30 Published:2017-01-17

摘要: 本研究旨在探讨大蒜素对实验性结肠癌大鼠的治疗作用及其作用机制。运用二甲肼30 mg/kg腹腔注射,每周注射1次,连续应用20周,成功建立实验性大鼠大肠癌模型,造模同时给予大蒜素注射液治疗。观察各组大鼠一般状态、脾脏指数、胸腺指数和组织病理学变化,酶联免疫吸附法(ELISA)检测血清中CD44V6和VEGF水平变化。Western blot法检测大肠组织中survivin、Cleaved Caspase-3和Cleaved Caspase-7的蛋白水平变化。实验结果显示第32周实验结束时,模型组大鼠平均体重与正常组相比显著降低(P<0.05)。大蒜素高、低剂量组大鼠体重与模型组相比显著增加(P<0.05)。大蒜素高、低剂量组大鼠平均胸腺指数、平均脾脏指数与模型组相比显著增高(P<0.05)。而大蒜素高剂量组胸腺指数、脾指数显著高于大蒜素低剂量组(P<0.05)。模型组肿瘤发生率、荷瘤数及肿瘤转移率均显著高于各给药组(P<0.05)。模型组大鼠血清CD44V6和VEGF水平显著高于正常组(P<0.05)。大蒜素高、低剂量组血清CD44V6和VEGF水平与模型组相比显著降低(P<0.05)。而与低剂量组相比,大蒜素高剂量组二项指标水平增加更为显著(P<0.05)。模型组大鼠大肠组织survivin、Caspase-3和Caspase-7表达水平显著高于正常组(P<0.05)。但与模型组相比,大蒜素高、低剂量组survivin表达水平显著降低,而Cleaved Caspase-3和Cleaved Caspase-7表达水平显著升高(P<0.05)。提示大蒜素对二甲肼诱导的实验性大鼠大肠癌具有良好的防治作用,可有效抑制大肠癌的发展及转移,其机制可能通过一方面增强大鼠体质,提高大鼠免疫功能,另一方面调节CD44V6和VEGF的水平来抑制肿瘤内血管的生成和浸润转移,同时抑制survivn基因的表达,上调Caspase-3和Caspase-7水平,从而促进癌细胞的凋亡。

关键词: 大蒜素, 大肠癌, 病理, 胸腺指数, 脾脏指数

Abstract: To study the therapeutic effect and mechanism of allicin on experimental colorectal cancer in rats.Experimental rat colon cancer model was successfully established by 30 mg/kg intraperitoneal injection of DMH,injection once a week,continuous application of 20 weeks,and the model was treated with allicin injection at the same time.The changes of general state,spleen index,thymus index,histopathological changes,CD44V6 and VEGF levels in serum and Survivin,Caspase-3 and Caspase-7 protein levels in colorectal tissues were compared before and after the treatment.At the end of the thirty-two weeks,the average weight of the model group was significantly lower than that of the normal group (P<0.05).The average weight of high and low dose allicin groups increased significantly compared with that of the model group (P<0.05).Thymus index and spleen index of high and low dose allicin group significantly increased compared with these of the model group (P<0.05).The thymus index and spleen index in high dose allicin group was significantly higher than that of low dose allicin group (P<0.05).The tumor incidence,tumor number and tumor metastasis rate in the model group were significantly higher than those in the other groups (P<0.05).The serum levels of CD44V6 and VEGF in model group were significantly higher than those in normal group (P<0.05).Serum CD44V6 and VEGF levels of allicin high and low dose group decreased significantly compared with the model group (P<0.05).Compared with the low dose allicin group,CD44V6 and VEGF levels of high dose allicin group increased more significantly (P<0.05).The expression level of survivin,Caspase-3 and Caspase-7 in the model group was significantly higher than that in the normal group (P<0.05).But compared with the model group,the survivin expression levels of high and low dose allicin group were significantly decreased,and expression level of Caspase-3 and caspase-7 were significantly increased (P<0.05).In conclusion,allicin had good prevention and cure function on experimental rats with colorectal cancer induced by dimethylhydrazine,which can effectively inhibit the development and metastasis of colorectal cancer,the mechanism may through enhancing rat physique,improving the immune function of rats and inhibiting tumor vessel formation and invasion and metastasis by regulating the expression of CD44v6 and VEGF,while allicin may inhibit the expression of survivin gene,upregulate Caspase-3 and caspase-7 level,so as to promote the apoptosis of cancer cells.

Key words: allicin, colorectal cancer, pathology, thymus index, spleen index

中图分类号: 

R255.4