新疆阿魏乙酸乙酯部位提取物对CT-26.WT原位移植瘤模型小鼠的抑瘤作用及机制研究  

Anti-tumor Effects of Ethyl Acetate Extract in Ferula sinkiangensis on CT-26.WT Orthotopic Transplantation Tumor Model Mice and Its Mechanism Study

作　　者：郭萍萍[1] 李伟[2] 张海英[1,2] GUO Pingping;LI Wei;ZHANG Haiying(College of TCM,Xinjiang Medical University,Urumqi 830000,China;Dept.of Pharmacy,the Affiliated TCM Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学中医学院,乌鲁木齐830000 [2]新疆医科大学附属中医医院药学部,乌鲁木齐830000

出　　处：《中国药房》2018年第23期3221-3226,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81660657);全国中药特色技术传承人才培训项目(No.国中医药人教函[2015]168号)

摘　　要：目的:研究新疆阿魏乙酸乙酯部位对CT-26.WT原位移植瘤模型小鼠的抑瘤作用,并探讨其作用机制。方法:将小鼠随机分为假手术组[溶剂(聚山梨酯80和食用油)]、模型组(溶剂)、顺铂对照组(5 mg/kg)和新疆阿魏乙酸乙酯部位提取物低、中、高剂量组(0.375、0.75、1.5 g/kg,以新疆阿魏乙酸乙酯部位提取物计),每组12只。除假手术组外其余各组小鼠建立CT-26.WT原位移植瘤模型,手术1周后灌胃给予相应药物,每隔2 d给药1次,连续给药10 d后,观察各组小鼠的体质量、瘤质量、肿瘤病理切片、脾指数,计算抑瘤率。采用流式细胞磁珠微阵列法(CBA)检测小鼠血清中白细胞介素12p70(IL-12p70)、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)、IL-6、单核细胞趋化蛋白1(MCP-1)、IL-10的水平。结果:与假手术组比较,其余各组小鼠成功建立原位移植瘤模型,体质量均明显降低(P<0.05),模型组小鼠血清中TNF-α、MCP-1、IL-6水平明显增加(P<0.05),IFN-γ和IL-10水平明显降低(P<0.05)。与模型组比较,顺铂对照组和新疆阿魏乙酸乙酯部位提取物低、中、高剂量组小鼠瘤质量明显降低(P<0.05),其抑瘤率分别为(62.96±12.54)%、(40.74±17.34)%、(45.93±16.74)%、(57.05±14.28)%,且肿瘤细胞排列松散,有丝分裂现象及肿瘤细胞的浸润减少,顺铂对照组和新疆阿魏乙酸乙酯部位提取物中、高剂量组小鼠的脾指数明显增加(P<0.05),所有给药组小鼠血清中IL-12p70、TNF-α、MCP-1、IL-10因子水平均明显增加(P<0.05),IL-6因子水平明显降低(P<0.05),仅新疆阿魏乙酸乙酯部位提取物高剂量组小鼠血清中IFN-γ因子水平明显增加(P<0.05)。结论:新疆阿魏乙酸乙酯部位提取物对CT-26.WT原位移植瘤模型小鼠具有抑瘤作用,其机制可能与增加IL-12p70、TNF-α、IFN-γ、MCP-1、IL-10水平和降低IL-6水平有关。OBJECTIVE：To study the anti-tumor effects of ethyl acetate extract of Ferula sinkiangensis on CT-26.WT orthotopic transplantated tumor model mice and investigate its related mechanism. METHODS：The mice were randomly divided into sham operation group [solvent （tween 80 and edible oil）],model group （solvent）,cisplatin control group （5 mg/kg）,low-dose,middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis（0.375,0.75,1.5 g/kg calculated,by ethyl acetate extract from F. sinkiangensis）,with 12 mice in each group. The mice model of CT-26.WT orthotopic transplantation tumor was established in each group except for sham operation group. They were given relevant medicine intragastrically,once every 2 days,for consecutive 10 d a week after surgery. The body weight,tumor weight,tumor pathological section and spleen index were observed in mice;inhibitory rate of tumor was calculated. The serum levels of IL-12p70,IFN-γ,TNF-α,IL-6,MCP-1 and IL-10 in rats were determined by flow cytometry microarray method （CBA）. RESULTS：Compared with sham operation group,orthotopic transplantation tumer model was established successfully in other groups,and body weight of mice was decreased significantly（P〈0.05）. Serum levels of TNF-α,MCP-1 and IL-6 were increased significantly in model group,while IFN-γ and IL-10 levels were decreased significantly（P〈0.05）. Inhibitory rate of tumor were（62.96±12.54）%,（40.74±17.34）%,（45.93± 16.74）%,（57.05±14.28）%,respectively. Compared with model group,tumor weight of mice were decreased significantly（P〈0.05）,cells were loosely arranged,as well as mitotic and infiltration of tumor cells decreased in cisplatin control group,low-dose,middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis. Spleen indexes of mice were increased significantly in cisplatin control group,middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis（P〈0.05）. Serum levels of IL-12p70,TNF-α,MCP-1

关 键 词：新疆阿魏 乙酸乙酯部位 结肠癌 原位移植瘤 流式细胞磁珠微阵列法 小鼠 细胞因子 抑瘤率 

分 类 号：R285.5[医药卫生—中药学]