摘要
目的观察蛇葡萄素与苯并芘合用对♂SD大鼠肝组织内CYP(cytochrome P450,CYP)和GST(glutathione S-transferase,GST)基因表达的影响。方法♂SD大鼠,蛇葡萄素(二氢杨梅素)250、500mg·kg-1,每日1次连续灌胃15d,d15模型组和2个给药组分别腹腔注射(ip)苯并芘100mg·kg-1。用逆转录-实时荧光定量PCR法检测肝组织内的CYP基因CYP1A1、CYP1A2、CYP1B1和GST基因GST-m1、GST-pi的表达情况。结果与空白组相比,苯并芘组(模型组)可明显诱导肝组织内的CYP1A1、CYP1A2、CYP1B1基因表达(P<0.01),分别是空白对照组的121倍、11倍、684倍,对谷胱甘肽-S转移酶基因GST-m1和GST-pi的表达有抑制趋势,分别是空白对照组的0.79倍和0.82倍;蛇葡萄素(二氢杨梅素)组+苯并芘组可明显诱导肝组织内的CYP1A1、CYP1A2、CYP1B1基因表达(P<0.01),分别是空白对照组的189和289倍、16.9和44.5倍、914和804倍,蛇葡萄素500mg.kg-1+苯并芘组明显诱导谷胱甘肽-S转移酶基因GST-m1和GST-pi的表达,分别是空白对照组的2.18倍(P<0.01)和2.12倍(P<0.05)。与苯并芘组(模型组)相比,蛇葡萄素250mg·kg-1+苯并芘组和蛇葡萄素500mg·kg-1+苯并芘组不影响CYP1B1的基因表达,但明显诱导CYP1A1的基因表达,分别是苯并芘组(模型组)的1.56倍(P>0.05)和2.39倍(P<0.05);明显诱导CYP1A2的基因表达,分别是苯并芘组(模型组)的1.53倍(P<0.05)和4.04倍(P<0.05);蛇葡萄素500mg.kg-1+苯并芘组明显诱导谷胱甘肽-S转移酶基因GST-m1和GST-pi的表达,分别是苯并芘组(模型组)的2.78倍(P<0.01)和2.57倍(P<0.05)。结论与苯并芘合用,蛇葡萄素(二氢杨梅素)可明显诱导CYP1A1、CYP1A2基因和谷胱甘肽-S转移酶基因GST-m1和GST-pi的表达。对CYP1B1基因无影响。表明蛇葡萄素与苯并芘合用可加速苯并芘代谢形成非致癌物而解毒和加速排泄。提示蛇葡萄素可对抗苯并芘的致癌作用。
Aim To examine the effects of ampelopsis （dihydromyricetin） and benzo （a） pyrene co-administration on the expression of cytoehrome P450 （CYP） genes and Glutathione S-Transferase （GST） genes in liver tissues of male Sprague-Dawley rats. Methods Rats were administered ampelopsis 250 or 500 mg·kg^-1 bw/d by gavage daily for 15 days, on the 15th day, the rats in the model group and the two groups treatment with ampelopsis were intraperitoneally （ip） given benzo（a）pyrene with 100 mg ·kg^-1 bw/d. The levels of gene expression of CYP1A1, CYP1A2, CYP1B1 and Glutathione S-Transferase M1 （GST-ml） and Glutathione S-Transferase pi （GST-pi） in the liver tissues of rats were examined by Quantitative real-time reverse-transcription polymerase chain reaction （quan- titative real time-RT-PCR） assays. Results Compared with the blank control, benzo （ a ） pyrene （ the model group） significantly increased mRNA expressions of CYP1A1 （ 121-fold,P 〈0. 01 ）, CYP1A2（ 11-fold,P 〈 0. 01 ）, CYP1B1 （684-fold,P 〈0. 01 ） , respectively, a inhibitory tendency was found on the expression of GST-ml （0.79-fold） and GST-pi （ 0. 82-fold） genes. When co-administrated with Benzo （a）pyrene, ampelopsis with 250 mg·kg^-1 and 500 mg·kg^-1 bw/d also significantly increased mRNA expressions of CYP1A1 （ 189-fold and 289-fold, P 〈 0.01 ）, CYP1A2 （ 16. 9-fold and 44.5-fold, P 〈 0. 01 ）, CYP1 B1 （684-fold and 804-fold） genes, respectively, 500 mg·kg^-1 dose of ampelopsis with benzo（a） pyrene gave a 2. 18-fold （P 〈0. 01 ）induction of GST-ml mRNA and 2. 12 fold （ P 〈 0. 05 ） induction of GST-pi mRNA. Compared with the model group [ benzo （a）pyrene goup], ampelopsis and benzo （a）pyrene co-administration had no effects on the expressions of CYP1 B1 gene, however, the two groups （co-administration） significantly increased the expressions of CYP1 A1 gene （ 1.56-fold, P〉0.05 and 2.39-fold,P 〈0.05）, and CYP1A2 gene（ 1.53-fold and 4. 04-fold ,P 〈 0.05 ）, respectively, and 500 mg·kg^-1 dose of ampelopsis with benzo （a） pyrene gave a 2.78-fold （ P 〈 0.01 ） induction of GST-ml gene expression and 2.57-fold （ P 〈 0. 05 ） in- duction of GST-pi gene expression. Conclusions When co-administered with Benzo （a） pyrene, ampelopsis can significantly induce the expressions of CYP1A1, CYP1A2, GST-ml, and GST-pi genes, but has no effect on CYP 1B1, which indicates ampelopsis can accelerate benzo （a）pyrene to form non-carcinogenic substance metabolites, then detoxicate and excrete quickly from the boby. Ampelopsis can protect the carcinogenic action induced by benzo（a） pyrene.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第7期860-865,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30660228)
广西高等学校优秀人才资助计划资助项目(No桂RC2007016)
