健脾理气方对人胃癌移植瘤小鼠TP、DPD和CYP3A4基因表达的影响

目的研究中药健脾理气方对人胃癌移植瘤小鼠5－氟尿嘧啶（5-FU）相关代谢酶及多种化疗药的共同代谢酶细胞色素P450酶（CYP3A4）基因调控的影响。方法将80只小鼠随机分为模型组、化疗组、中药组及化疗加中药组，每组20只。小鼠左腋窝皮下接种MKN-8肿瘤细胞悬液，复制人胃癌移植瘤小鼠模型。模型组和中药组于接种瘤株2天后分别给予生理盐水或健脾理气方0.25 mL灌胃，均每天2次，连续10天。化疗组和化疗加中药组于接种2天后分别给予生理盐水或健脾理气方0.25 mL灌胃，每天2次，连续5天；接种7天后给予5-FU 20 mg/（kg·d）腹腔注射，每天1次，连续5天。采用RT-PCR法检测各组移植瘤组织胸腺嘧啶磷酸化酶（thymidine phosphorylase，TP）、双氢嘧啶脱氢酶（dihydropyrimidine dehydrogenase，DPD）和CYP3A4的mRNA表达。结果与模型组及化疗组比较，中药组及化疗加中药组小鼠移植瘤组织中TP、CYP3A4 mRNA表达水平明显升高，DPD mRNA表达水平明显降低，差异均有统计学意义（P<0.01）。化疗加中药组与中药组TP、DPD、CYP3A4 mRNA表达水平比较，差异均无统计学意义（P>0.05）。结论健脾理气方能够通过上调小鼠移植瘤组织中TP、CYP3A4的mRNA表达水平，同时抑制DPD的mRNA表达水平，从而促进5-FU在肿瘤组织中的活化以及抑制5－FU的分解失活，提高化疗疗效。

英文摘要:

Objective To study the effect of Jianpi Liqi Recipe （JLR） on 5-fluorouracil （5-FU） relevant metabolic enzymes and CYP3A4 （the same enzyme of many chemotherapeutics） of mice with human gastric cancer transplanted tumor. Methods Totally 80 mice were randomly divided into the model group， the chemotherapy group， the JLR group， and the combination group （using chemotherapy combined JLR）， 20 in each group. The human gastric cancer transplanted tumor mouse model was duplicated by hypodermic inoculating MKN-8 tumor cell suspension from the left armpit. Physiological saline or JLR was given to those in the model group or the JLR group at 0.25 mL each time， twice daily by gastrogavage from the 2nd day after transplantation. Mice in the chemotherapy group were given 0.25 mL physiological saline， twice daily by gastrogavage 2 days after transplantation， for 5 days in succession， and then they were peritoneal injected with 5-FU at the daily dose of 20 mg/kg， once daily for 5 days in succession from the 7th day of transplantation. Those in the combination were given 0.25 mL JLR， twice daily by gastrogavage， for 5 days in succession， and then they were peritoneal injected with 5-FU at the daily dose of 20 mg/kg， once daily for 5 days in succession from the 7th day of transplantation. The mRNA expressions of thymidine phosphorylase （TP）， dihydropyrimidine dehydrogenase （DPD）， and CYP3A4 were detected using RT-PCR. Results Compared with the model group and the chemotherapy group， mRNA expressions of TP and CYP3A4 obviously increased， mRNA expression of DPD obviously decreased in the JLR group and the combination group （P<0.01）. There was no statistical difference in mRNA expressions of TP， DPD， and CYP3A4 between the JLR group and the combination group （P>0.05）. Conclusion JLR could promote the activation of 5-FU， suppress the decomposition and inactivation of 5-FU in the tumor tissue of mice， and improve the chemotherapeutic efficacy through up-regulating mRNA expressions of TP and CYP3A4， and suppressing the mRNA expression of DPD.

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