基于抑制TCIPA研究黄芪莪术配伍抗肿瘤转移机制

Study on the anti-tumor metastasis mechanism of compatibility of Astragalus and Rhizoma Curcumae based on inhibition of TCIPA

目的通过观察黄芪莪术配伍对荷瘤模型小鼠肺转移和抑制肿瘤细胞血小板聚集的作用,阐述黄芪莪术配伍在此环节抑制肿瘤转移的作用机制。方法 40只C57小鼠随机分为正常对照组、模型组、阿司匹林组、黄芪莪术配伍组(简称中药组),每组10只;除正常对照组外,其他各组接种Lewis肿瘤细胞制备荷瘤鼠模型,并于接种后次日开始连续21 d给予相应干预,麻醉解剖后,经腹主动脉取血,抗凝离心处理后,Elisa法检测血浆凝血酶原、纤维蛋白原、P-选择素、组织因子(tissue factor,TF)、整合蛋白ɑⅡbβ3的含量;处死后,取出肺脏,肉眼观察双肺表面超过1 mm结节数目。结果与模型组相比,给药组转移结节数显著减少(P <0. 05),中药组虽少于阿司匹林组,但差异无统计学意义;瘤重指数和抑瘤率,各组瘤重和瘤重指数差异无统计学意义(P> 0. 05);纤维蛋白原含量,与正常对照组比较,各组均明显升高(P <0. 05),各给药组与模型组比较,差异无统计学意义;凝血酶原含量,各组之间多重比较,差异无统计学意义(P> 0. 05);组织因子含量,模型组比正常对照组明显升高(P <0. 05),各给药组均比模型组明显降低(P <0. 05),且与正常对照组比较差异无统计学意义,中药组低于阿司匹林组但差异无统计学意义; P-选择素的含量,与正常对照组比较,模型组明显升高(P <0. 05),而各给药组均低于模型组(P <0. 05),中药组低于阿司匹林组但差异无统计学意义;整合蛋白ɑⅡbβ3的含量,与正常对照组比较,各组均升高(P <0. 05),阿司匹林组、中药组与模型组虽然无统计学差异,但中药组最接近正常组。结论益气活血法抗肿瘤常用黄芪莪术配伍能抑制Lewis荷瘤小鼠肿瘤转移,其作用机制与其在肿瘤细胞诱导血小板聚集(Tumour cell-induced platelet aggregation,TCIPA)环节中降低血浆组织因子含量、降低血小板活化程度有关。

Objective To observe the effect of compatibility of Astragalus and Rhizoma Curcumae on lung metastasis and inhibition of platelet aggregation in tumor-bearing mice to explain its anti-tumor metastasis mechanism.Methods Forty C57 mice were randomly divided into normal control group,model group,aspirin group and compatibility of Astragalus and Rhizoma Curcumae group(Chinese medicine group)with 10 mice in each group.Except normal control group,other groups were inoculated with Lewis tumor cells to establish tumor-bearing mice model.The next day after inoculation,corresponding intervention was given for 21 days.The mice were dissected after anesthesia.The blood was taken from abdominal aorta and treated with anticoagulant centrifugation.The levels of prothrombin,fibrinogen,P-selectin,tissue factor TF and integrinɑⅡbβ3 in plasma were detected by Elisa method.The lungs were taken out and the number of nodules on the surface of both lungs was observed with naked eyes.Results Compared with the model group,the number of metastatic nodules in the administration groups was significantly reduced(P<0.05).Although the number of metastatic nodules in the Chinese medicine group was less than that in the aspirin group,there was no significant difference between the two groups.There was no significant difference in tumor weight index and inhibition rate between among groups(P>0.05).Compared with the normal control group,the content of fibrinogen in each group was increased significantly(P<0.05),and there was no significant difference between the model group and the administration group.There was no significant difference in prothrombin content among groups(P>0.05).Compared with the normal control group,the content of tissuefactor in the model group increased significantly(P<0.05).Compared with the model group,the content of tissue factor in the administration groups was decreased significantly(P<0.05),but there was no significant difference among the normal control group and the administration groups.The content of tissue factor in the Chinese medicine group was lower than that in the aspirin group,but there was no significant difference.Compared with the normal control group,the content of integrinɑⅡbβ3 in other groups was increased significantly(P<0.05).There was no significant difference in the content of integrinɑⅡbβ3 among the aspirin group,Chinese medicine group and model group,but the content of integrinɑⅡbβ3 in Chinese medicine group was closest to the normal group.Conclusion The combination of compatibility of Astragalus and Rhizoma Curcumae can inhibit tumor metastasis in mice bearing Lewis tumor.The mechanism is related to the decrease of tissue factor content in plasma tissue factor and platelet activation in TCIPA.