氰戊菊酯对细胞色素P450 2B1/2B2的诱导  

Inductive effect of fenvalerate on cytochrome P450 2B1/2B2 1

作　　者：贺锡雯[1] 张伟华[1] 吕京[1] 崔涛[1] 谢广云[1] 

机构地区：[1]中国预防医学科学院劳动卫生与职业病研究所

出　　处：《中国药理学与毒理学杂志》1999年第3期222-226,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金

摘　　要：１５只ＳＤ大鼠随机分为氰戊菊酯（Ｆｅｎ）组（１２０ｍｇ·ｋｇ－１·ｄ－１×７，ｉｇ），苯巴比妥（ＰＢ）诱导组（８０ｍｇ·ｋｇ－１·ｄ－１×３，ｉｐ）及溶剂对照组（给予Ｆｅｎ组等体积的二甲亚砜，处理同Ｆｅｎ组）．应用不连续ＳＤＳ－ＰＡＧＥ电泳分离细胞色素Ｐ４５０，用ＣＯ差示光谱法和细胞色素Ｃ还原法测定Ｐ４５０含量及ＮＡＤＰＨ－细胞色素Ｐ４５０还原酶活性，用ＣＹＰ２Ｂ１／２Ｂ２抗体及ＣＹＰ３Ａ１／３Ａ２抗体进行Ｗｅｓｔｅｒｎ印迹法分析，用免疫组化和半定量ＲＴ－ＰＣＲ等技术观察Ｆｅｎ影响大鼠脑，肝组织细胞色素Ｐ４５０亚型的特异性．结果显示，与溶剂对照组相比Ｆｅｎ可使脑和肝中Ｐ４５０含量及ＮＡＤＰＨ－Ｐ４５０还原酶活性增高；Ｐ４５０２Ｂ１／２Ｂ２增加，Ｐ４５０３Ａ１／３Ａ２未见改变；Ｐ４５０２Ｂ１／２Ｂ２ｍＲＮＡ含量相应增加．由于正常大鼠脑，肝组织中Ｐ４５０２Ｂ１／２Ｂ２表达很低，Ｆｅｎ对该亚型Ｐ４５０的诱导可能会干扰机体对内，外源化合物的正常代谢，从而产生毒作用．Three groups of 15 Sprague Dawley rats (5 rats per group) were administrated with fenvalerate (120 mg·kg 1 ·d 1 ×7, ig), or phenobarbital (80 mg·kg 1 ·d 1 ×3, ip) or DMSO (vehicle group, treated as same as the fenvalerate group), respectively. The certain subtypes of cytochrome P450s induced by fenvalerate in the rat brain and liver were identified by steps such as SDS PAGE, determination of the contents of P450s and the activities of NADPH cytochrome P450 reductase, detection of P450 2B1/2B2 and 3A1/3A2 protein by immunohistochemical analysis or by Western blot, and semiquantitative analysis of CYP 2B1/2B2 mRNA expression by RT PCR. The results showed that fenvalerate increased both the contents of P450s and the activity of NADPH cytochrome P450 reductase in the brain and liver compared with control. The induced P450 protein by fenvalerate was 2B1/2B2 subtypes, whereas P450 3A1/3A2 did not change. Meanwhile, the increased expression of CYP 2B1/2B2 mRNAs was observed. Because of the very limited expression of P450 2B1/2B2 in the brain and liver of normal rats, the increased contents of P450 2B1/2B2 may interfere in the metabolism of endobiotic and exobiotic and induce their toxicity.

关 键 词：氰戊菊酯 脑 肝 细胞色素 P450 毒理学 农药 

分 类 号：R994.3[医药卫生—毒理学]