磷甲酸钠在鸭体内对鸭乙型肝炎病毒的抑制作用  

Inhibitory effect of trisodium phosphonoformate (PFA) on duck hepatitis B virus(DHBV) DNA in vivo

作　　者：陈湘红[1] 陈鸿珊[1] 

机构地区：[1]中国医学科学院医药生物技术研究所

出　　处：《中华实验和临床病毒学杂志》1997年第3期277-281,共5页Chinese Journal of Experimental and Clinical Virology

摘　　要：以鸭乙型肝炎病毒（ＤＨＢＶ）静脉感染雏鸭为模型，分组腹腔注射磷甲酸钠（ＰＦＡ）２５０ｍｇ、１２５ｍｇ、６２．５ｍｇ／ｋｇ及生理盐水，观察治疗后鸭血清中ＤＨＢＶＤＮＡ及ＤＨＢｓＡｇ的动态变化，并检测肝、肾、脾及胰中ＤＨＢＶＤＮＡ的分布；提取肝脏中超螺旋ＤＮＡ（ＳＣＤＮＡ），检测ＰＦＡ对ＤＨＢＶＤＮＡ复制的影响。结果表明：ＰＦＡ治疗第７天到第２１天，１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组对ＤＨＢｓＡｇ有显著的抑制作用；１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组治疗第１４、２１天对血清中ＤＨＢＶＤＮＡ有显著的抑制作用；１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组治疗第２１天肝及肾中ＤＨＢＶＤＮＡ明显下降；２５０ｍｇ／ｋｇ剂量组治疗２１天对ＤＨＢＶ感染鸭肝细胞内ＤＨＢＶＲＣＤＮＡ、ＬＤＮＡ及ＳＣＤＮＡ的合成有明显抑制作用。可见，最大剂量２５０ｍｇ／ｋｇＰＦＡ每天２次，治疗２１天，对ＤＨＢＶ感染鸭血清中ＤＨＢｓＡｇ、血清及肝、肾中ＤＨＢＶＤＮＡ都有抑制作用，对脾、胰中ＤＨＢＶＤＮＡ抑制不明显。提示该药能抑制ＤＨＢＶ感染，但未能清除病毒，故停药后可出现反跳现象。This paper described that DHBV infected ducklings were given with PFA 250mg, 125mg, 62 5mg/kg b.i.d for 21 days intraperitioneally (ip) and dynamics of duck hepatitis B virus DNA (DHBV DNA) and duck hepatitis B surface antigen (DHBsAg) were detected in serum and distribution of DHBV DNA was tested in liver, kidney, pancreas and spleen. Supercoiled DNA (SC DNA) extracted from liver was analysed with Southern blot. The results showed that PFA in a dose of 125mg and 250mg/kg inhibited significantly the serum DHBsAg; doses of 125mg and 250mg/kg inhibited the serum DHBV DNA from 14 to 21 days, and dose of 250mg/kg inhibited the serum DHBV DNA earlier even at 7 days after being given with PFA. Doses of 125mg and 250 mg/kg inhibited obviously DHBV DNA in liver and kidney, but no inhibiton was found in spleen and pancreas. The replication of DHBV DNA in liver of ducklings treated with PFA in a dose of 250 mg/kg for 21 days showed that the PFA inhibited significantly the synthesis of linear DNA (L DNA), relaxed circular DNA (RC DNA) and SC DNA. But DHBsAg and DHBV DNA in serum and DHBV DNA in liver, kidney, pancreas and spleen after treated with PFA for 21 days were still present, this meant that PFA treatment didnt clear off the virus genome in infected ducklings, the “rebounding” of DHBV appeared after cessation of the PFA treatment.

关 键 词：乙型肝炎病毒 磷甲酸钠 鸭模型 DNA 病毒 

分 类 号：R373.21[医药卫生—病原生物学]