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热毒宁注射液对大鼠肝脏CYP450酶的影响

材料写作网    时间: 2021-04-02 04:06:07     阅读:次     手机站

[摘要]研究热毒宁注射液对大鼠肝脏CYP450酶酶活性及其mRNA表达水平的影响。将SD大鼠腹腔注射7 d后,处死,制备大鼠的肝微粒体,与探针药物共孵育,利用LC/MS法测定各同工酶特异性底物在大鼠肝微粒的代谢产物的生成量,间接反映各同工酶的活性。应用荧光定量PCR技术考察热毒宁注射液对大鼠肝脏CYP450酶mRNA表达水平的影响。结果显示,酶活性方面,热毒宁注射液与空白组比较可抑制CYP2B1,2C12,2C13,2D2的酶活性,诱导CYP3A1的酶活性,对CYP1A2酶活性无明显影响。mRNA表达方面,热毒宁注射液对CYP2B1,3A1,1A2,2C11,2D1,2E1 mRNA的表达具有诱导作用。通过对上述结果分析,可以看出热毒宁注射液在酶活性和mRNA水平均对CYP3A1具有显著的诱导作用,与大环内酯类抗生素合用时可能会出现不良反应;对CYP2B1,2C12,2C13,2D2的酶活性均具有抑制作用,与其他药物联合用药时要充分考虑可能出现的药物相互作用或潜在风险。

[关键词]热毒宁注射液;细胞色素P450酶;Cocktail探针法;荧光定量PCR技术

Effects of Reduning injection on activity of hepatic microsomal

CYP450 isozymes in rats

ZHANG Yun-yan1, XU Wang-yanjun2, TANG Xiang-lin1*, MA Zeng-chun1, WANG Yu-guang1, LIANG Qian-de1,

TAN Hong-ling1, XIAO Cheng-rong1, WANG Zhen-zhong3, XIAO Wei3, GAO Yue1*

(1. Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China;

2. Anhui Medical University, Hefei 230032, China;

3.Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China)

[Abstract]To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450(CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time qu...



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