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人肝CYP3A参与了山冈橐吾碱的代谢及其肝毒性代谢物的形成(英文) 被引量:5
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作者 柳晓泉 林鸽 +1 位作者 王广基 钱之玉 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2002年第1期15-20,共6页
目的 在体外研究山冈橐吾碱在人肝微粒体内的代谢及参与其代谢的主要的CYP4 5 0酶 ,探讨其代谢致毒机理。方法 采用人肝微粒体研究山冈橐吾碱的主要代谢方式和代谢物。在体外运用CYP4 5 0酶的选择性抑制剂和cDNA表达的人肝CYP4 5 0酶 ... 目的 在体外研究山冈橐吾碱在人肝微粒体内的代谢及参与其代谢的主要的CYP4 5 0酶 ,探讨其代谢致毒机理。方法 采用人肝微粒体研究山冈橐吾碱的主要代谢方式和代谢物。在体外运用CYP4 5 0酶的选择性抑制剂和cDNA表达的人肝CYP4 5 0酶 ,探讨其对山冈橐吾碱的代谢及肝毒性的吡咯代谢物形成的影响及参与山冈橐吾碱代谢的主要的CYP4 5 0酶。结果 山冈橐吾碱在人肝微粒体内的主要代谢物为肝毒性的吡咯代谢物 :去氢倒千里光裂碱 ,7 谷胱甘肽基 去氢倒千里光裂碱 ,7,9 二谷胱甘肽基去氢倒千里光裂碱和山冈囊吾酸。CYP4 5 0特异性抑制剂α 萘黄酮 (抑制CYP1A2 )、黄胺苯吡唑 (抑制CYP2C)、奎尼丁 (抑制CYP2D6 )和二乙基二硫代氨基甲酸钠 (抑制CYP2E1)对山冈橐吾碱的代谢无明显的影响。但CYP3A的特异性抑制剂酮康唑和三乙酰竹桃霉素可以显著地抑制山冈橐吾碱的代谢及其吡咯代谢物和结合型吡咯物的形成。此外 ,在cDNA表达的人肝CYP3A4的温孵液中 ,山冈橐吾碱被代谢成相应的吡咯代谢物 ,而山冈橐吾碱在cDNA表达的人肝CYP1A2、CYP2C9、CYP2D6和CYP2E1温孵液中无代谢。结论 山冈橐吾碱在人肝微粒体内的主要代谢方式是形成肝毒性吡咯代谢物 ,CYP3A作为主要的CYP4 5 0酶参与了山冈橐吾碱的代谢及其肝毒性吡咯代谢? 展开更多
关键词 山冈橐吾碱 微粒体 转化 肝毒性代谢物 CYP3A4
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Effect of Ganduqing Granule on metabolic disorder and liver dysfunction in patients with chronic hepatitis B
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作者 You-Ping Liu Bo Li +3 位作者 Xiao-Dong Wang Shao-Ping Mi En-Ze Liu Mei Wei 《Traditional Medicine Research》 2017年第4期161-168,共8页
Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 p... Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 patients with CHB before and after the treatment with GDQG were measured for the alterations in liver function and metabolites,using the method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry.Results:Patients with CHB developed severe liver dysfunction,which was associated with the higher plasma levels of 8 metabolites when compared with those of the normal control(P<0.05).Interestingly,after treatment with GDQG for 3 weeks,the 8 metabolites were significantly reduced(P<0.05).Among them,glycochenodeoxycholate-3-sulfate,glycochenodeoxycholic acid-3-glucuronide,taurochenodeoxycholic acid,and 7b-hydroxy-3-oxo-5b-cholanoic acid were associated with the metabolism of bile acids,while 3b,16a-dihydroxyandrostenone sulfate,lysophosphatidylcholine(C18:3),and lysophosphatidylethanolamine(C22:1)were related to the metabolism of lipids.2,6-Diamino-4-hydroxy-5-N-methylformamidopyrimidine was related to hepatic oxidative stress.Meanwhile,liver damage in patients was greatly reduced.Conclusion:Treatment with GDQG has improved liver function of patients with CHB through the possible mechanism of adjusting the metabolic disorders related to lipids,bile acids,and oxidative stress. 展开更多
关键词 Ganduqing Granule Chronic hepatitis B PLASMA METABOLITES
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