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| 摘要: |
| 目的研究辛伐他汀(simvastatin, SV)对大鼠肝脏药物代谢酶活性的影响。方法大鼠口服给予SV，qd×7，超速离心法分离肝微粒体，一氧化碳示差光谱法测定细胞色素P450(CYP)含量，以红霉素、苯胺、CDNB、利尿酸、7-羟基-4-甲基香豆素和对羟基联苯为底物分别测定肝微粒体红霉素脱甲基酶(CYP3A4)、苯胺羟化酶(CYP2E1)、谷胱甘肽-S-转移酶(glutathione S transferase, GST)及其π亚型 (πGST)、尿苷二磷酸葡萄糖醛酸转移酶(uridine diphosphoglucuronyl transferase, UGT1和UGT2)活性。结果大鼠口服给予SV可明显降低大鼠肝微粒体CYP含量及CYP3A4活性，对CYP2E1则没有显明影响。同时,SV 则可显著增高大鼠肝微粒体GST、πGST及UGT1和UGT2活性。结论SV可降低大鼠肝微粒体CYP3A4活性，而增高肝微粒体Ⅱ相代谢酶的活性。 |
| 关键词: 辛伐他汀 药物代谢酶 肝脏 |
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| Effects of Simvastatin on Drug-metabolizing Enzyme of Liver Microsome in Rats |
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WU Dongfang1，ZHANG Lei2，LIU Ping1
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| Abstract: |
| OBJECTIVE To investigate the effects of simvastatin (SV) on drug-metabolizing enzyme of liver microsome in rats. METHODS Rats were given SV by oral administration，qd 7. Liver microsome was prepareded by ultracentrifugation. Cytochrome P450 (CYP) content was determined by CO-difference spectrum. Erythromycin, aniline, 1-chloro-2, 4-dinitrobenzene (CDNB), ethacrynic acid, 7-hydroxy-4-methylcoumarin and 4-Hydroxybiphenol were used as the substrates for the determination of CYP3A4，CYP2E1, glutathione S transferase(GST) and πGST, uridine diphosphoglucuronyl transferase (UGT1 and UGT2) activities. RESULTS After SV oral administration, CYP content and CYP3A4 activity were significantly decreased in rats, but no difference of CYP2E1 activity was found. Meanwhile, SV administration caused a remarkable increase in liver microsome GST, πGST, UGT1 and UGT2 activities. CONCLUSION SV increased in CYP3A4 activity and reduced Ⅱ phase drug-metabolized enzyme in rats. |
| Key words: simvastatin drug-metabolized enzyme liver |
