论文部分内容阅读
研究地西泮、苯巴比妥、普萘洛尔和西咪替丁对地西泮氧化代谢的影响及其药酶蛋白的初步分析，应用ＨＰＬＣ，ＳＤＳ聚丙烯酰胺凝胶电泳和薄层扫描测定地西泮及其代谢物，并对大鼠肝微粒体和酶蛋白进行分离和含量测定。结果表明地西泮、普萘洛尔和西咪替丁使肝微粒体中Ｐ４５０含量明显降低。地西泮和普萘洛尔明显抑制地西泮Ｃ３羟化活性，大剂量普萘洛尔尚能抑制地西泮Ｎ脱甲基。苯巴比妥明显诱导Ｐ４５０生成，增强地西泮Ｎ脱甲基和Ｃ３羟化酶活性及分子量为５１，０００和５９，０００的电泳蛋白带，而地西泮、普萘洛尔则呈抑制作用。并发现，地西泮Ｎ脱甲基酶活性和分子量为５９，０００蛋白含量呈线性相关（Ｐ＜０．０５），而Ｃ３羟化酶活性则与５１，０００蛋白含量呈线性相关（Ｐ＜０．０１）。因此地西泮Ｃ３羟化代谢可能与５１，０００的Ｐ４５０酶蛋白有关，而Ｎ脱甲基代谢则可能与５９，０００的Ｐ４５０酶蛋白有关。
To study the effects of diazepam, phenobarbital, propranolol and cimetidine on the oxidative metabolism of diazepam and its preliminary analysis of the drug-eluting enzyme protein, HPLC, SDS-polyacrylamide gel electrophoresis and thin layer Scanning determination of diazepam and its metabolites, and liver microsomes and enzyme protein were isolated and assayed. The results show that diazepam, propranolol and cimetidine liver microsomal P 450 content was significantly reduced. Diazepam and propranolol significantly inhibit the activity of diazepam C3 hydroxylation, high-dose propranolol can inhibit diazepam N demethylation. Phenobarbital significantly induced P 450 generation, increased diazepam N demethylation and C3 hydroxylase activity and molecular weight of 51,000 and 59,000 electrophoretic protein bands, and diazepam, Seoul was inhibited. And found that diazepam N-demethylase activity and molecular weight of 59,000 protein content was linearly related (P <0.05), and C3 hydroxylase activity and 51,000 protein content was linearly correlated ( P <0.01). Therefore, diazepam C3 hydroxylation metabolism may be related to 51,000 P 450 enzyme protein, and N demethylation metabolism may be related to 59,000 P 450 enzyme protein.