[关键词]
[摘要]
目的 探讨大蒜新素在体内对鼠巨细胞病毒 (m urine cytom egalovirus,MCMV)感染小鼠的预防及治疗作用。方法 建立 BAL B/c小鼠 MCMV重组病毒 (插入 L ac Z基因 )性肝炎模型,采用 X- gal染色测定β- gal在肝、肾及肺组织中的表达。 70只雌性 BAL B/c小鼠随机分为大蒜新素预防 +治疗组 (n=2 0 ),大蒜新素治疗组(n=2 0 ),更昔洛韦治疗组〔6 0 m g/(kg· d),n=10〕,安慰剂组 (n=10 )及空白对照组 (n=10 )。其中前两组又各均分为低、高剂量组〔2 5,75 m g/(kg· d)〕,检测血浆丙氨酸转氨酶 (AL T)水平和评估肝组织组织学活动性指数(HAI),并用原位杂交法检测肝组织中 MCMV DNA水平。结果 大蒜新素预防 +治疗组及治疗组与安慰剂组相比较,AL T、肝脏 HAI评分及 MCMV DNA杂交的积分光密度均明显降低 (P<0 .0 5 ),与更昔洛韦治疗组相比无显著差异 ;大蒜新素预防用药及加大用药剂量并不能显著降低 AL T、肝脏 HAI评分及 MCMV DNA积分光密度水平。结论 大蒜新素能减轻 MCMV性肝炎模型鼠肝功能损害,改善肝脏病理变化和降低肝组织内病毒 DNA负荷量,其治疗效果与更昔洛韦无显著差异,大蒜新素预防用药及加大用药剂量不能增加其病毒抑制效应。
[Key word]
[Abstract]
Object To investigate the phylactic and therapeutic ability of allitridin to murine cytomegalovirus (MCMV) in vivo. Methods A MCMV hepatitis model using BABL/c mice was established with recombination of MCMV RM461 strain (LacZ gene carried). X-gal staining was used to detect the express of β-gal in liver, kidney and lung. Seventy female mice were allocated randomly into allitridin phylaxy+therapy group (n=20), allitridin therapy group (n=20), Ganciclovir therapy group 〔60 mg/(kg·d)〕 (n=10), placebo treated group (n=10) and control group (n=10). The first two groups were devided into two subgroups: low and high dosage 〔25, 75 mg/(kg·d)〕 subgroups. Drug was initially used 48 h before virus infection in phylaxy+therapy group, and 48 h after virus infection in therapy group. After treated for 14 d or 18 d, all mice were sacrificed, alanine aminotransferase (ALT) and histological activity index (HAI) of liver tissue slides were recorded, MCMV DNA load was also detected by in situ hibirdization on liver tissue slides. Results ALT, HAI and integral photo density of MCMV DNA of all allitridin-treated groups were significantly reduced when comparied with placebo group (P0.05) and no significant deviation comparied with Ganciclovir therapy group; ALT, HAI and MCMV DNA accumulated optical density had not been significantly reduced by phylaxic using and higher dosage of allitricin. Conclusion Allitricin can alleviate liver lesion, lighten liver histological pathology change and reduce MCMV DNA load of liver tissue in MCMV hepatitis model, its effect is similar to that of Ganciclovir. The phylaxic usage and higher dosage seem contribute little to allitridin's anticytomegalovirus activity in vivo.
[中图分类号]
[基金项目]
国家自然科学基金资助项目(30070928)