脾肾阳虚大鼠脾中Ⅰ相和Ⅱ相药物代谢酶活性变化的研究

摘要

[目的]观察脾肾阳虚状态下大鼠脾脏中主要Ⅰ相和Ⅱ相药物代谢酶活性的改变.[方法]采用连续17d灌胃大黄水煎液同时注射氢化可的松的方法复制大鼠脾肾阳虚模型,观察脾脏中6种Ⅰ相代谢酶(CYP2C 19、CYP2D6、CYP2C9、CYP1A2、CYP2C8、CYP3A4)和4种Ⅱ相代谢酶[苯酚磺基转移酶(PST)、尿苷二磷酸葡醛酸转移酶1(UGT1)、谷胱甘肽转移酶(GST)、雌激素硫酸转移酶(SULT1E1)]的活性变化.[结果]模型组PST、UGT1、GST、SULTlE1活性显著低于正常组(P＜ 0.05或P＜ 0.01);CYP1A2活性显著高于正常组(P＜0.01),而CYP2C 19、CYP2D6、CYP2C8、CYP3A4、CYP2C9等酶的活性无显著变化(P＞0.05).[结论]脾肾阳虚状态下脾脏药物代谢酶特别是Ⅱ相代谢酶的活性会发生显著改变.%Objective To study the changes of activities of phase Ⅰ and Ⅱ drug-metabolic enzymes in the spleen of rats with spleen-kidney yang deficiency syndrome.Methods The rat model of spleen-kidney yang deficiency syndrome was established by gastric gavage of Radix et Rhizoma Rhei decoction combined with injection of hydrocortisone for 17 continuous days.And then we detected the activities of 6 kinds of phase Ⅰ drug-metabolic enzymes of CYP2C19,CYP2D6,CYP2C9,CYP1A2,CYP2C8,CYP3A4,and 4 kinds of phase Ⅱ drugmetabolic enzymes of phenol sulfotransferase (PST),uridine diphosphate glucuronosyl transferase 1 (UGT1),glutathione transferase (GST),estrogen sulfotransferase (SULT1E1) in the spleen.Results Compared with the normal control group,the activities of PST,UGT1,GST and SULT1E1 in the model group were significantly decreased (P ＜ 0.05 or P ＜ 0.01),and the activity of CYP1A2 was significantly increased (P ＜ 0.01),while CYP2C19,CYP2D6,CYP2C8,CYP3A4,CYP2C9 enzymes showed no obvious changes(P ＞ 0.05).Conclusion The activities of splenic drug-metabolic enzymes,in particular the phase Ⅱ enzymes,are significantly varied under the state of spleen-kidney yang deficiency.