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当归贝母苦参丸加味方对荷瘤小鼠H22肝癌肿瘤组织MMP13和bFGF表达的影响     被引量:16

Effects of Dangguibeimukushen pill on expressions of MMP13 and bFGF on H22 hepatocarcinoma xenograft mice

文献类型:期刊文献

中文题名:当归贝母苦参丸加味方对荷瘤小鼠H22肝癌肿瘤组织MMP13和bFGF表达的影响

英文题名:Effects of Dangguibeimukushen pill on expressions of MMP13 and bFGF on H22 hepatocarcinoma xenograft mice

作者:刘春萍[1];李海龙[2];张艳[2];吴红彦[2];王宏伟[3]

第一作者:刘春萍

机构:[1]甘肃省酒泉市第二人民医院,735000;[2]甘肃省中医方药挖掘与创新转化重点实验室/甘肃省中药新产品创制工程实验室,兰州730000;[3]甘肃中医药大学附属医院,兰州730020

第一机构:甘肃省酒泉市第二人民医院,735000

年份:2017

卷号:38

期号:2

起止页码:153

中文期刊名:国际检验医学杂志

外文期刊名:International Journal of Laboratory Medicine

收录:CSTPCD

基金:甘肃省高等学校科研资助项目(2013A-088);甘肃省中药药理与毒理学重点实验室开放基金资助项目[ZDSYS-ZZKJ-2013(B)-005]

语种:中文

中文关键词:当归贝母苦参丸加味方;肝癌;荷瘤小鼠;MMP13;bFGF

外文关键词:Dangguibeimukushen pill; hepatocellular carcinoma; tumor bearing mice; MMP13; bFGF

摘要:目的研究当归贝母苦参丸加味方对H22荷瘤小鼠瘤组织基质金属蛋白酶13(MMP13)和成纤维细胞生长因子2(bFGF)表达的影响。方法建立H22荷瘤小鼠模型进行体内抗肿瘤试验,将60只荷瘤小鼠随机分为模型组,顺铂阳性对照组,当归贝母苦参丸加味方高、低剂量组,当归贝母苦参丸加味方高、低剂量联合顺铂组,连续灌胃给药14d,观察肿瘤生长情况以及小鼠一般情况,肿瘤大体标本及HE染色后组织形态观察;RT-qPCR和免疫组织化学技术分别检测肿瘤组织中MMP13和bFGF的表达。结果大体观察剥离的肿瘤瘤体发现,模型组与中药低剂量组瘤体较大,瘤体内有溃烂,包膜基本完整;各治疗组瘤体较模型组相比较小,但包膜不完整,有不同程度溃烂,剥离易出血,当归贝母苦参丸加味方高、低剂量联合顺铂组瘤体小,包膜完整,肿瘤溃烂较少;HE染色病理形态观察发现,各治疗组结缔组织明显,细胞稀疏程度增加,坏死癌细胞数目增加。RT-qPCR检测显示,与模型组相比,各用药组中MMP13和bFGF mRNA的表达量均降低,差异有统计学意义(P<0.05);免疫组化检测显示,MMP13和bFGF在当归贝母苦参丸加味方高、低剂量联合顺铂组中蛋白着色变浅,呈弱阳性表达,当归贝母苦参丸加味方高、低剂量联合顺铂组较单独用药蛋白表达量低,差异有统计学意义(P<0.05)。结论当归贝母苦参丸加味方可以在mRNA和蛋白水平下调荷瘤小鼠肿瘤组织中MMP13和bFGF的表达,进而抑制肿瘤侵袭和血管生成,发挥抑瘤减毒增效目的。
Objective To study the effects of supplemental Dangguibeimukushen pill prescription on the expressions of MMP13 and bFGF in tumor tissues on H22 hepatoma bearing mice.Methods H22 hepatoma bearing mice was employed to carry out antitumor experiment in vivo in this study.A total of 60 mice were randomly divided into model group,DDP positive control group,low and high dosage of supplemental Dangguibeimukushen pill treatment group,supplemental Dangguibeimukushen pill combined with DDP group.In each gruop,gastric infusion was performed continuously 14 d.The tumor growth and the general conditions of mice were recorded.After the last administration of gavages orally treatment,all mice were anaesthetized and killed by cervical dislocation method to obtain completely tumor tissue for further HE staining measure and detection of MMP13 and bFGF in tumor tissue with the method of RT-qPCR and immunohistochemistry.Results The tumor volume of model group and low dosage of supplemental Dangguibeimukushen pill treatment group were larger than that of other groups,futhermore,ulceration were found inside tumor,and basic integrity were observed of tumor capsule.However,in all the treatment groups,the tumor volume was relatively smaller,and the capsule of tumor was incomplete,ulceration of different degrees and bleeding when tumor was peeled off.In combination groups,the tumor volume was much smaller,and the tumor had incomplete capsule and less ulceration inside.Pathological observation showed that connective tissue was found inside tumor,cells were sparsely spread and the number of necrosis cancer cells were increased in all treatment groups.RT-qPCR detection showed that the mRNA expression of MMP13 and bFGF in each treatment group were decreased comparing with the model group,and the difference was statistically significant(P〈0.05).Immunohistochemical detection showed that the expression of MMP13 and bFGF in the combined group were less colored and weakly positive expression comparing with the positive group or the pure Chinese medicine treatment group,the difference was statistically significant(P〈0.05).Conclusion Dangguibeimukushen pill could downregulate the expression of MMP13 and bFGF of tumor tissue in H22 hepatocarcinoma xenograft mice at mRNA and protein levels,and played a vital role in inhibiting cancer invasion and angiogenesis,reducing toxics and side effects and enchancing its efficiency.

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