龙胆生品及龙胆酒制品给药后龙胆苦苷在大鼠主要器官组织中的浓度分布

目的：探讨龙胆酒制前后龙胆苦苷在大鼠主要器官组织中的浓度分布，为进一步研究龙胆药材的炮制方法与其功效的相关性提供科学依据。方法：将60只大鼠随机分为龙胆生品组和龙胆酒制品组，分别灌胃给药龙胆生品及龙胆酒制品（0.63 g·kg^-1），于6个不同时间点（15、30、60、120、240和360 min）处死大鼠，每时间点每组各5只大鼠。采用液相色谱-质谱联用（HPLC-MS）法测定各组不同时间点龙胆苦苷在大鼠心、肝、脾、肺、肾和脑组织中的质量浓度。结果：龙胆苦苷在50~20000 μg·L^-1范围内线性关系良好（r ≥ 0.9969）；该方法的精密度和稳定性相对标准偏差（RSD）均小于15%；回收率为77.4%~87.2%，RSD小于15%，符合化学药物非临床药代动力学研究技术指导原则；HPLC-MS法检测，龙胆苦苷在大鼠体内分布比较广泛，在大鼠心、肝、脾、肺、肾和脑等组织中均有分布；30min时龙胆生品及酒制品中龙胆苦苷质量浓度在大鼠心脏组织中达到峰值，60 min时在肝、脾和肺组织中达到峰值；与龙胆生品组比较，龙胆酒制品组龙胆苦苷在大鼠肝、肺和肾组织中的药-时曲线下面积（AUC_0→360min）明显增加（P<0.01），在脑组织中小幅增加（P<0.01），在心和脾组织中稍有降低（P<0.05）。结论：龙胆酒制后能够促进龙胆苦苷在肝和肾等器官中的吸收利用，改变龙胆苦苷在大鼠主要器官组织中的浓度分布。

Concentration distribution of gentiopicrin in main organs and tissues of rats after administration of gentian raw products and gentian wine products

Objective: To investigate the concentration distribution of gentiopicrin in the main organs and tissues of the rats before and after the preparation of gentian wine,and to provide the scientific basis for further discussion on the correlation between the processing methods and the efficacy of gentian. Methods: Sixty rats were randomly divided into gentian raw products group and gentian wine products group with 5 rats per group at each time point.The rats were given gentian raw products and gentian wine products (0.63 g·kg^-1) intragastrically and killed at 6 different time points (15, 30, 60, 120, 240 and 360min).The mass concentrations of gentiopicrin in heart,liver, spleen,lung,kidney and brain tissues of the rats in varrious groups were measured by high-performance liquid chromatography-mass spectrometry(HPLC-MS) method at different time points. Results: The linear relationship of gentiopicrin in the range of 50-20000 μg·L^-1 was good (r ≥ 0.996 9).The relative standard deviation (RSD) of precision and stability of this method was less than 15%.The recovery rate was 77.4%-87.2%,and RSD was less than 15%,which was in accordance with the technical guidelines for the study of non-clinical pharmacokinetics of chemical drugs. The results of HPLC-MS method showed that gentiopicrin was widely distributed in the rats,including heart,liver, spleen,lung,kidney and brain tissues and so on.At the point of 30 min,the gentiopicrin concentrations from gentian raw products and wine products reached the peak in heart tissue,and reached the peak values in liver spleen and lung and kidney tissues at 60 min.Compared with the gentian raw products,the area under curve (AUC_{0→360 min}) of gentiopicrin in the gentian wine products in liver,lung and kidney tissues were significantly increased (P<0.01),the AUC_{0→360 min} in brain tissue was increased (P<0.01),but the AUC_{0→360 min} in heart and spleen tissues were slightly decreased(P<0.05). Conclusion: Gentian can promote the absorption and utilization of gentiopicrin in liver,kidney and other organs,and change the concentration distribution of gentiopicrin in the main organs and tissues of the rats by processing with wine.