三种免疫抑制剂对HBV质粒感染小鼠HBV复制的影响

发布时间：2018-01-03 17:14

本文关键词：三种免疫抑制剂对HBV质粒感染小鼠HBV复制的影响　出处：《实用肝脏病杂志》2015年04期 　论文类型：期刊论文

【摘要】：目的应用小鼠模型评价3种临床常用的免疫抑制剂对乙型肝炎病毒(HBV)复制的影响。方法利用高压水注射法将HBV质粒p AAV/HBV1.2导入Balb/C小鼠肝内,建立小鼠HBV复制模型;将Balb/C小鼠随机分成4组,每组10只,分别给予生理盐水(Saline)、FK506、DEX和CYP处理。1w后,将供体C57BL/6小鼠皮瓣移植至上述经免疫抑制剂或生理盐水处理的Balb/C小鼠,皮肤移植后继续使用上述免疫抑制剂或生理盐水至观察期结束。采用电化学免疫发光法检测血清HBs Ag、HBs Ab和HBc Ab水平,采用Real-time PCR法检测血清病毒载量。结果FK506、地塞米松和环磷酰胺处理小鼠移植皮瓣的存活时间分别为(21.50±3.09)d、(21.50±3.09)d和(21.40±1.52)d,分别较生理盐水处理组(8.67±1.86)d明显延长[P=0.037、P=0.000和P=0.000];FK506处理组小鼠HBV复制及其抗体产生与对照组无显著性差异,地塞米松处理组在药物处理期间能维持病毒复制,但停药后病毒DNA和HBs Ag迅速下降至检测水平以下,至观察终点仍未检出HBs Ab和HBc Ab阳性,环磷酰胺能明显延长小鼠HBV复制的持续时间,即使在停药后16 w血清HBV DNA和HBs Ag均维持在较高水平,HBc Ab和HBs Ab持续阴性。结论环磷酰胺而非FK506处理可在Balb/C小鼠模型中建立HBV持续复制模型。
[Abstract]:Objective to evaluate the effect of three immunosuppressants on hepatitis B virus (HBV) in mice. Methods HBV plasmid p AAV/HBV1.2 was injected into the liver of Balb/C mice by high pressure water injection. Mouse HBV model was established. Balb/C mice were randomly divided into 4 groups (n = 10 in each group). The mice were treated with FK506DEX and CYP for 1 week, respectively. The donor C57BL / 6 skin flap was transplanted to the above Balb/C mice treated with immunosuppressant or normal saline. After skin transplantation, the immunosuppressive agents or normal saline were used until the end of the observation period. The levels of serum HBs Ag-HBs Ab and HBc Ab were detected by electrochemical immunoluminescence assay. Real-time PCR method was used to detect the viral load in serum. Results FK506. The survival time of transplanted skin flap treated with dexamethasone and cyclophosphamide was 21.50 卤3.09 and 21.40 卤1.52 days, respectively. It was significantly longer than that of normal saline treatment group (8.67 卤1.86g / d). [P0. 037, P0. 000 and P0. 000; There was no significant difference in HBV replication and antibody production between FK506 treated group and control group. Dexamethasone treatment group could maintain virus replication during drug treatment. However, the DNA and HBs Ag of the virus decreased rapidly below the detection level after withdrawal of the drug, and no positive HBs Ab and HBc Ab were detected at the end of observation. Cyclophosphamide significantly prolonged the duration of HBV replication in mice, and serum HBV DNA and HBs Ag were maintained at a higher level even at 16 weeks after withdrawal. Conclusion cyclophosphamide instead of FK506 treatment can establish HBV continuous replication model in Balb/C mice.
【作者单位】：华中科技大学同济医学院附属协和医院感染病科;德国埃森大学医学院病毒研究所;
【基金】：国家传染病防治科技重大专项课题(2008ZX10002011)
【分类号】：R373.21
【正文快照】： 乙型肝炎病毒(Hepatitis B virus,HBV)感染仍然是一个重要的全球性公共卫生问题。我国是HBV感染的高发区,人群HBs Ag携带率为7.18%[1]。免疫抑制药物的使用常可导致HBV感染的再激活或导致HBV的持续感染,但不同药物对HBV感染再激活的影响不同[2,3]。因此,有必要利用合适的动物

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