基于药物代谢酶途径的何首乌“时-毒-效”变化规律研究  

Study on the Change Law of “Time-Toxicity-Effect” for Polygonum Multiflorum Based on Drug Metabolic Enzyme Pathway

作　　者：李炯侠 郭延丽 刘巧 高峰[2] 董泰玮 陈琳 李瑞 卫培峰[2] LI Jiongxia;GUO Yanli;LIU Qiao(3201 Hospital,Xianyang Shaanxi 723000,China;Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi 712046,China)

机构地区：[1]三二〇一医院,陕西汉中723000 [2]陕西中医药大学,陕西咸阳712046 [3]陕西中医药大学附属医院,陕西咸阳712000

出　　处：《四川中医》2021年第11期48-53,共6页Journal of Sichuan of Traditional Chinese Medicine

基　　金：陕西省科技厅自然科学基础项目(编号:2016JM8058);国家自然科学基金项目(81373988)。

摘　　要：目的:观察何首乌不同炮制时间对正常小鼠和肝损伤小鼠肝脏的损伤作用及肝脏药物代谢酶mRNA表达的影响,初步探讨其肝损伤发生机理。方法:分别给正常小鼠和肝损伤小鼠以何首乌不同炮制品,观察其对肝脏的损伤及保护作用;不同炮制方法炮制的何首乌灌胃小鼠后对血液生化指标的影响采用微板法检测;分析小鼠肝脏的病理变化则采用HE染色法;用RT-PCR方法检测何首乌不同炮制品对大鼠肝脏药物代谢酶CYP2E1、CYP3A、CYP1A2mRNA相对表达量的的影响。结果:灌胃何首乌不同炮制品4周后的正常小鼠,肝脏均出现了不同程度的损伤,其中生首乌与清蒸8h组小鼠肝损伤显著,然而灌胃何首乌炮制时间越长的小鼠肝损伤程度小;各给药组的CYP2E1、CYP3A、CYP1A2mRNA酶的表达量较空白组均显著下降,且延长炮制时间各表达量呈逐渐下降趋势。而给肝损伤小鼠灌胃给药后,阳性药组的小鼠肝损伤出现明显好转,各何首乌给药组无明显好转,但是,灌胃何首乌炮制时间越长的肝损伤小鼠,均出现了好转的趋势。结论:何首乌对正常小鼠可引起不同程度的肝脏损伤,且随炮制时间延长,肝损伤程度有所降低,调节机体药物代谢酶CYP2E1、CYP3A、CYP1A2mRNA表达量可能是其毒性机理;而对肝损伤小鼠虽有好转的趋势,但没有显著性差异。Objective: To observe the effect of different processing time of Polygonum multiflorum on liver injury and the expression of drug metabolizing enzyme mRNA in liver of normal mice and liver injury mice, and to explore the mechanism of liver injury. Methods: Different processed products of Polygonum multiflorum were given to normal mice and mice with liver injury, respectively, and their liver injury and protective effects were observed. Effect of Polygonum multiflorum processed by different processing methods on blood biochemical indexes in mice after intragastric administration of Polygonum multiflorum by microplate method. HE staining was used to analyze the pathological changes of mouse liver. The effect of different processed products of Polygonum multiflorum on the relative expression of drug metabolizing enzymes CYP2 E1,CYP3 A and CYP1 A2 mRNA in rat liver were detected by RT-PCR method. Results: After oral administration of different processed products of Polygonum multiflorum for 4 weeks, the normal mice showed different degrees of liver injury, in which the liver injury was significant in the group of Polygonum multiflorum and steaming for 8 hours, but the longer the processing time of Polygonum multiflorum was given to the stomach, the less the degree of liver injury was. The expression of CYP2 E1,CYP3 A and CYP1 A2 mRNA in each treatment group was significantly lower than that in the blank group, and the expression of each enzyme decreased gradually when the processing time was prolonged. After intragastric administration, the liver injury of mice in the positive group was significantly improved, and there was no significant improvement in the each Polygonum multiflorum group. However, the longer the processing time of Polygonum multiflorum, the liver injury mice showed a trend of improvement. Conclusion: Polygonum multiflorum can cause different degrees of liver injury in normal mice, and with the prolongation of processing time, the degree of liver injury decreases, regulating the expression of drug m

关 键 词：何首乌 炮制时间 肝损伤 保肝机理 

分 类 号：R285.5[医药卫生—中药学]