Cocktail法评价敌敌畏对大鼠CYP450亚型酶活性的影响

科研成果详情

题名	Cocktail法评价敌敌畏对大鼠CYP450亚型酶活性的影响
其他题名	Effect evaluation of dichlorvos on CYP450 isoforms activity in rats by cocktail method
作者	李君桦 1; 吴海亚2; 陈东鑫 3; 耿培武 4; 庄开赞 5; 周华 3
发表日期	2018-08-25
发表期刊	中国卫生检验杂志影响因子和分区
语种	中文
原始文献类型	学术期刊
关键词	敌敌畏鸡尾酒法大鼠细胞色素P450 聚合酶链式反应
其他关键词	Dichlorvos ; Cocktail ; Rat ; CYP450 ; PCR
摘要	目的用Cocktail探针药物法评估敌敌畏对大鼠CYP450酶代谢活性的影响。方法将大鼠随机分为敌敌畏组和对照组。敌敌畏组给予腹腔注射12.5 mg/kg敌敌畏,对照组给予等体积生理盐水。然后灌胃给予5种探针药物(安非他酮、美托洛尔、非那西丁、睾酮和甲苯磺丁脲),用超高效液相色谱串联质谱法测定血浆探针浓度;同时分离肝脏,用PCR法测定5种亚型酶mRNA的表达量。结果敌敌畏组CYP1A2、CYP2D1和CYP3A2的AUC明显高于对照组,差异有统计学意义(P<0.05),而对CYP2B1和CYP2C11的药代动力学无显著影响;CYP2D1和CYP3A2的mRNA表达水平均显著降低(P<0.05),CYP1A2的mRNA表达水平明显升高,差异有统计学意义(P<0.05),而CYP2C11和CYP2B1的mRNA表达水平与对照组比较差异无统计学意义(P>0.05)。结论结合PCR结果,腹腔注射敌敌畏可以抑制大鼠CYP2D1和CYP3A2的酶活性。
其他摘要	Objective In this work, a cocktail method was employed to evaluate the effects of dichlorvos on the metabolic activities of CYP450. Methods The rats were divided into dichlorvos group and control group. The dichlorvos group rats were given12. 5 mg/kg dichlorvos by intraperitoneal administration, and the control group were given normal saline. The probe drugs ( bupropion, metroprolol, phenacetin, testosterone and tolbutamide) were given to rats by intragastric administration, and the ultra high performance liquid chromatography tandem mass spectrometry ( UPLC-MS/MS) method was used to determined probe plasma concentrations. At the same time, livers were isolated and the mRNA expression levels of five CYP450 isoforms were determined by PCR. Results AUC of CYP1 A2, CYP2 D1 and CYP3 A2 in the dichlorvos group increased significantly ( P ＜ 0. 05), while pharmacokinetics difference for CYP2 B1 and CYP2 C11 had no significant changes. Expression levels of CYP2 D1 and CYP3 A2 mRNA declined significantly, with the difference statistically significant ( P ＜ 0. 05), while that of CYP1 A2 mRNA increased significantly, with the difference statistically significant ( P ＜ 0. 05). There was no statistical significance on the difference in expression levels of CYP2 C11 and CYP2 B1 mRNA by comparing dichlorvos group with control group ( P＞ 0. 05). Conclusion Combined with PCR results, intraperitoneal administration of dichlorvos could inhibit the activities of CYP2 D1 and CYP3 A2 of rats.
资助项目	温州市科技计划项目（Y20150178）;宁波市科技计划项目（2016A610188;2016A610192;2017A610265）;浙江省中西医结合学会科研项目（2016LYK010）
ISSN	1004-8685
卷号	28 期号:16 页码:1961-1964
页数	4
收录类别	CNKI ; 万方 ; 维普 ; PKU ; 北大核心 ; ISTIC
URL	查看原文
CNKI分类号	R595.4
万方分类号	R363(病理学)
维普分类号	R363
CN号	41-1192/R
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/46338
专题	附属第二医院
作者单位	1.温州市中心医院; 2.温州医科大学附属第二医院; 3.宁波李惠利医院; 4.丽水市人民医院; 5.奉化人民医院
推荐引用方式 GB/T 7714	李君桦,吴海亚,陈东鑫,等. Cocktail法评价敌敌畏对大鼠CYP450亚型酶活性的影响[J]. 中国卫生检验杂志,2018,28(16):1961-1964.
APA	李君桦, 吴海亚, 陈东鑫, 耿培武, 庄开赞, & 周华. (2018). Cocktail法评价敌敌畏对大鼠CYP450亚型酶活性的影响. 中国卫生检验杂志, 28(16), 1961-1964.
MLA	李君桦,et al."Cocktail法评价敌敌畏对大鼠CYP450亚型酶活性的影响".中国卫生检验杂志 28.16(2018):1961-1964.

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