苯丙氨酸二肽类化合物Y101对DHBV-DNA的影响  

Effects of phenylalanine dipeptide compound Y101 on DHBV-DNA

作　　者：刘青川[1,2] 王晨吟[1] 何书桃[1] 张伟[1] 卢苇[1] 刘军[1] 黄正明[1] 

机构地区：[1]解放军302医院药学部,北京100039 [2]贵州百灵企业集团制药股份有限公司,贵州安顺561000

出　　处：《中国药理学通报》2012年第10期1389-1393,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部"国际合作"新药基金资助项目(No2008DFB30110);国家科技重大专项资助项目(No2011ZX09102-009-002);国家自然科学基金项目(No30760292)

摘　　要：目的探讨苯丙氨酸二肽类化合物Y101对感染鸭乙肝病毒的北京雏鸭体内外DHBV-DNA表达的影响。方法90只感染DHBV的北京雏鸭随机分为对照组、Y101剂量组和拉米夫定组,各组雏鸭于给药前(d 0)、给药5 d(d 5)、10d(d 10)及停药后3 d(P 3)经腿胫静脉取血,分离血清,斑点杂交法测定鸭血清中DHBV-DNA的含量;利用灌流法分取感染鸭乙肝病毒的北京雏鸭的原代肝细胞,采用QuickEx-tract DNA Extraction Soln 1.0提取鸭原代肝细胞Y101剂量组、拉米夫定对照组和正常对照组细胞内和细胞上清中的DHBV-DNA,用TaqMan探针实时荧光定量法检测DHBV-DNA含量,观察Y101对其抑制作用。结果 Y101对体内外DHBV-DNA都具有良好的抑制作用,体内0.05、0.025 g.kg-1剂量组抑制作用明显,体外80、60 mg.L-1剂量组抑制作用最强,DNA含量明显下降(P<0.05)。结论Y101可以有效的抑制DHBV-DNA的表达,抗病毒作用明显。Aim To evaluate the effects of phenylalanine dipeptide compound Y101 on DHBV-DNA in vitro and vivo.Methods Beijing ducklings infected with duck hepatitis B virus were divided into control,Y101,Lamivudine groups.Serum was collected at 0,5 and 1 0 days after drugs were administered and at 3 days after drugs were withdrawn from vena cruralis.The presence of DHBV-DNA in serum was detected by dot blot hybridization;Duck primary hepatocytes were collected from Beijing ducklings infected with duck hepatitis B virus by perfusion.DHBV-DNA in cells and supernatants was extracted from Y101,Lamivudine and normal control groups with the use of QuickExtract DNA Extraction Soln 1.0.The contents of DHBV-DNA were determined with Taqman probe Quantitative RealTime PCR method and the inhibitory rates were calculated.Results Y101 could obviously inhibit DHBVDNA in vitro and vivo.The effective dosages were 0.05 g.kg-1,0.025 g.kg-1 groups in vivo and 80 mg.L-1,60 mg.L-1 groups in vitro,respectively.The content of DNA decreased significantly.Conclusion Y101 has a siginificant inhibiory effect on DHBV-DNA in vitro and vivo.

关 键 词：苯丙氨酸二肽类化合物Y101 鸭原代肝细胞 斑点杂交 细胞培养 DHBV-DNA 荧光定量PCR 

分 类 号：R-332[医药卫生] R342.3