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目的 通过检测细胞色素氧化酶CYP2E1的表达和活性变化,从分子水平探讨中药配伍禁忌“十八反”理论中甘遂配伍甘草的药理机制。方法 利用RT PCR检测大鼠肝脏CYP2E1mRNA水平;通过Westernblot检测大鼠肝脏CYP2E1蛋白表达;采用高效液相色谱(HPLC)法测定CYP2E1酶活性。结果 甘遂组、甘草组和甘遂甘草配伍组均明显诱导大鼠肝脏CYP2E1的表达与活性上升,并发现甘草组和甘遂甘草配伍组对CYP2E1活性的诱导作用显著高于甘遂组。结论 甘遂可能通过诱导肝脏CYP2E1的表达与活性上升,促使其所含的前致癌物质和前毒物转化成为致癌物和毒物,导致对机体的毒性作用;甘遂甘草配伍使用时,甘草对CYP2E1活性的诱导能力更强,故而甘草可促进甘遂所含前致癌物质和前毒物转化成为致癌物和毒物的过程,并导致对机体毒性作用的增强,从而表现出“十八反”中药物配伍禁忌的特征。
Objective To investigate the pharmacological mechanism of compatibility of Ganzi and Gancao with Glycyrrhiza uralensis Fisch. Methods The level of CYP2E1 mRNA in rat liver was detected by RT PCR, and the expression of CYP2E1 protein in liver of rats was detected by Western blot. The activity of CYP2E1 was determined by high performance liquid chromatography (HPLC). Results The expressions and activities of CYP2E1 in the rat liver were significantly increased in the Ganzi group, the licorice group and the Ganzi Gancao compatibility group, and the induction of CYP2E1 activity in the licorice group and the Ganzi Gancao compatibility group was significantly higher than that in the Ganzi group. Conclusion Ganzi may induce the expression and activity of CYP2E1 in the liver, which promotes the conversion of pre-carcinogens and protoxins contained in the liver into carcinogens and toxins, resulting in toxic effects on the body. The compatibility of licorice against CYP2E1 when used in combination with kangasin and licorice The induction ability is stronger. Therefore, licorice can promote the conversion of pre-carcinogens and pro-toxins contained in kansui into carcinogens and toxins, and lead to an increase in the toxic effects of the body, thereby showing the incompatibility of drugs in the “eighteen anti-inhibition”. Characteristics.