引经药桔梗对顺铂在原位肺癌移植瘤裸鼠体内分布的影响

Effects of platycodon grandiflorum on the distribution of cisplatin in orthotopic lung cancer transplantation of nude mice

目的:探讨桔梗(PG)的引经作用对顺铂(DDP)在裸鼠体内的组织分布的影响。方法:60只裸鼠经胸腔穿刺法注射A549构建裸鼠原位肺癌移植模型,随机分为:模型组、DDP 3mg/kg组、DDP+桔梗1g/kg组、DDP+桔梗2g/kg组、DDP+桔梗4g/kg组,连续给药30天。取血浆及各脏器,采用高效液相色谱法测定顺铂的药物浓度。PT-q PCR测定肺中AQP1、AQP5、P-gp的mRNA表达量。结果:桔梗显著增加顺铂在肺脏、脾脏中药物浓度(桔梗1g/kg、2g/kg、4g/kg剂量增加幅度分别为31.1%、43.0%、33.0%;51.0%、30.0%、18.9%);并显著降低了顺铂在肝脏、心脏、小肠中的药物浓度。与DDP组比较,联用桔梗1g/kg、2g/kg、4g/kg剂量组对P-gp基因表达分别降低32.62%、28.88%、65.78%。结论:桔梗可能通过降低肺中P-gp表达量增强了顺铂在裸鼠肺组织的药物分布。

Objective： To investigate the influence of platycodon grandiflorum’s guide action on the tissue distribution of cisplatin in nude mice.Methods： A549 cells were injected into pleural to establish an orthotopic lung cancer model. Animals were randomly divided into several groups as follows： the model group,cisplatin（ DDP） group,DDP ＋ low,middle,high doses of PG groups. Animals in PG groups were ig given 1,2 and 4 g/kg,per day,DDP groups with 3 mg/kg i. p twice a week,while they in the control group were given same amount of water（ ig） and normal saline（ NS,ip）. The treatment continued for 30 days. After mice were sacrificed,interested tissues were collected and weighted. High performance liquid chromatography（ HPLC） method was used to detect the concentration of cisplatin in tissues of nude mice,then RT-q PCR method was used to detect mRNA expressions of AQP1,AQP5 and P-gp in tomor tissues. Results： PG decreased the concenration of cisplatin in nude mice,however,PG 1,2 and 4 g/kg significantly increased concentrations of DDP in lungs and spleens by 31. 1% 、43. 0% 、33. 0%; 51. 0% 、30. 0% 、18. 9% respectively（ P 〈 0. 05）. Meanwhile,it significantly decreased concentrations of DPP in livers,hearts and small intestines. Compared with DPP group,low,medium and high doses of PG decreased the expression of P-gp mRNA by 32.62%,28. 88% and 65. 78%,respectively. Conclusion： The distribution of cisplatin in lung tissues of nude mice was enhanced by platycodon grandiflorum,which may be related to the decrease of p-gp expression in the lung tissue.