基于“甘能缓”的理论对甘草配伍黄药子减毒机理的研究

Clinical practice has shown the exact effect of Dioscorea bulbifera by treating cancer, however high doses or long-term use of Dioscorea bulbifera and Dioscorea bulbifer apreparations can cause acute poisoning and accumulation of liver injury, as in the clinical application of Dioscorea bulbifera increasing the resulting drug-induced liver and even death situation around. The combining use of Dioscorea bulbifera and Diosorea Dulbifera is based on traditional Chinese medicine theory that Gan slow detoxification, impassioned phasecompatibility of the killing, fear attenuated relative to the practice, and the clinical and laboratory have already shown that licorice can reduce the liver toxicity of Dioscorea bulbifera. The project trying to explore the mechanism of the liver injury attenuated by bulbifera and the compatibility of licorice from the sub-cellular and gene level to observing the changes of expression of CYP450 isoforms, gene mRNA expression of rat liver CYP1A2, CYP2E1,and protein expression of CYP1A2, CYP2E1 influenced by licorice combined with Dioscorea bulbifera.To provide experimental basis for the safety and rational use of Dioscorea bulbifera and other difficult cases of toxic traditional Chinese medicine in clinical and develop the property theory of" gan can relieve spasm and slow detoxification " and Compatibility theory of"mutual detoxication、mutual restraint".

临床实践表明黄药子治疗肿瘤有确切疗效，但是，大量或长期服用黄药子及含黄药子的制剂可引起急性中毒及蓄积性肝损伤，随着黄药子在临床的应用日益增加，由此导致的药物性肝损害、甚至死亡的情况屡有发生。黄药子配伍甘草是根据传统中药甘缓解毒、七情配伍之相杀、相畏减毒的实践与理论，临床和实验已表明甘草能降低黄药子的肝毒性。本项目拟通过黄药子配伍甘草后对CYP450亚型的影响、对大鼠肝脏CYP1A2、CYP2E1基因mRNA表达和CYP1A2、CYP2E1蛋白质表达的影响，从亚细胞和基因水平探讨黄药子肝损伤和配伍甘草减毒的机制，以期为有毒中药的配伍减毒、中医临床安全与合理应用黄药子等有毒中药治疗疑难病症提供实验依据，丰富和发展中药甘缓解毒的药性理论以及相杀、相畏的配伍理论。

临床实践表明黄药子治疗肿瘤有确切疗效，然黄药子苦寒，攻散性强，治疗瘿瘤、疮疡肿毒用药时间长，易耗正气，易引起急性中毒及蓄积性肝损伤，随着黄药子在临床的应用日益增加，由此导致的药物性肝损害、甚至死亡的情况屡有发生。黄药子配伍甘草是根据传统中药甘缓解毒、七情配伍之相杀、相畏减毒的实践与理论，临床和实验已表明甘草具保护肝脏作用，能降低黄药子的肝毒性。本项目通过大鼠肝脏CYP1A2、CYP2E1基因mRNA表达和CYP1A2、CYP2E1蛋白质表达的影响，从基因水平探讨黄药子肝损伤和配伍甘草减毒的机制。在mRNA水平上，黄药子组显著诱导CYP1A2、CYP2E1基因的表达，配伍甘草后表达降低，差异具有统计学意义（P<0.05）。在蛋白表达水平上，与黄药子组比较，配伍组肝脏CYP1A2、CYP2E1蛋白的阳性表达指数降低（P<0.05或P<0.01）。研究结果显示，甘草可能通过抑制大鼠肝脏CYP1A2、CYP2E1的mRNA和蛋白表达，对黄药子致肝损伤具有一定的保护作用。