發(fā)布時(shí)間：2018-03-29 01:28

  本文選題：細(xì)胞色素肝藥酶　切入點(diǎn)：雞尾酒法　出處：《蚌埠醫(yī)學(xué)院》2014年碩士論文

【摘要】：目的：通過“雞尾酒探針?biāo)幬锓ā苯⒁环N快速、簡(jiǎn)便、靈敏的HPLC方法評(píng)價(jià)異甘草酸鎂對(duì)大鼠細(xì)胞色素P450代謝酶活動(dòng)的影響。 方法：選取SPF級(jí)SD大鼠隨機(jī)分為單劑量組、多劑量組及實(shí)驗(yàn)對(duì)照組。探針?biāo)幬锛敖o藥劑量分別為咪達(dá)唑侖10mg/kg、右美沙芬5mg/kg、奧美拉唑10mg/kg、茶堿25mg/kg、氯唑沙宗50mg/kg、雙氯芬酸5mg/kg。異甘草酸鎂注射液的給藥劑量為20mg/kg。通過腹腔注射給予探針?biāo)幬�，尾靜脈注射給予異甘草酸鎂注射液。給藥后于一定的時(shí)間段從大鼠眼底靜脈叢取血0.5ml置于肝素化的離心管中，通過高效液相色譜法檢測(cè)血漿中探針?biāo)幬锏难帩舛�，測(cè)得的數(shù)據(jù)經(jīng)DAS2.0軟件處理得出相關(guān)藥動(dòng)學(xué)參數(shù)。然后通過t檢驗(yàn)分析各組之間差異。 結(jié)果：大鼠體內(nèi)異甘草酸鎂聯(lián)合用探針?biāo)幬锝o藥后，右美沙芬、茶堿、雙氯芬酸及奧美拉唑藥動(dòng)學(xué)參數(shù)無顯著性變化。單劑量組的探針?biāo)幬镞溥_(dá)唑侖及多劑量組的探針?biāo)幬飱W美拉唑在大鼠體內(nèi)某些藥動(dòng)學(xué)參數(shù)發(fā)生顯著性變化。 結(jié)論：異甘草酸鎂注射液能夠誘導(dǎo)大鼠體內(nèi)肝藥酶CYP2E1的活性及抑制大鼠肝藥酶CYP3A4的活性。對(duì)大鼠體內(nèi)細(xì)胞色素肝藥酶CYP2D6、CYP1A2、CYP2C19及CYP2C9無顯著性影響，，提示我們?cè)谂R床合用異甘草酸鎂與CYP2E1及CYP3A4代謝的底物藥物時(shí)應(yīng)注意藥物的代謝性相互作用。
[Abstract]:Objective: to establish a rapid, simple and sensitive HPLC method to evaluate the effect of magnesium isoliganate on the activity of cytochrome P450 metabolic enzyme in rats. Methods: SPF SD rats were randomly divided into single dose group. The dosage of the probe was 10 mg / kg of midazolam, 5 mg / kg of dextromethorphan, 10 mg / kg of omeprazole, 25 mg / kg of theophylline, 50 mg / kg of clozoxazone, 5 mg / kg of diclofenac and 20 mg / kg of magnesium isoglycyrrhizate. Injected with probe drugs, Magnesium isoglycyrrhizinate was injected into the tail vein. 0.5ml was taken from the fundus venous plexus of rats at a certain time and placed in heparinized centrifuge tube. The blood concentration of the probe drug in plasma was detected by high performance liquid chromatography (HPLC). The relevant pharmacokinetic parameters were obtained by DAS2.0 software, and then the differences among the groups were analyzed by t-test. Results: dextromethorphan, theophylline, dextromethorphan and theophylline were treated with magnesium isoglycyrrhizinate in rats. The pharmacokinetic parameters of diclofenac and omeprazole were not significantly changed. Conclusion: magnesium isoglycyrrhizinate injection can induce the activity of hepatic drug enzyme CYP2E1 and inhibit the activity of rat liver drug enzyme CYP3A4 in vivo, but has no significant effect on cytochrome hepatic enzyme CYP2D6, CYP1A2, CYP2C19 and CYP2C9 in rats. It is suggested that we should pay attention to the metabolic interaction of magnesium isoglycyrrhizinate with substrates of CYP2E1 and CYP3A4.
【學(xué)位授予單位】：蚌埠醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965

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