中文摘要：

目的建立CXCR3基因敲除小鼠慢性乙型肝炎病毒复制模型。方法繁育CXCR3基因敲除小鼠,并抽提组织DNA进行聚合酶链反应及凝胶电泳鉴定基因型。CXCR3基因敲除小鼠纯合子9只与野生型C57BL/6小鼠9只同时高压水注射pAAV/HBV1.2质粒,按既定时间点采血检测HBsAg、HBeAg、HBV DNA,以及取肝组织行免疫组织化学检测HBcAg表达。结果本实验室繁殖的CXCR3基因敲除小鼠均为纯合子基因型。在pAAV/HBV1.2质粒转染后第1天,CXCR3基因敲除小鼠与野生型C57BL/6小鼠血清HBsAg水平分别为1134.69±244.42和1759.63±881.20（P=0.096）;第4天分别为5305.29±1395.06和7493.29±658.63（P=0.003）;第15天分别为1615.04±1187.16和1536.19±1046.02（P=0.905）;第40天为229.45±79.27和228.19±295.02（P=0.996）;第1天血清HBeAg水平分别为6.65±1.50和20.61±4.03（P=0.000）;第4天为6.33±1.61和9.79±2.31（P=0.007）;第15天为3.52±1.97和2.85±0.74（P=0.425）;第40天为1.28±0.06和1.90±1.01（P=0.431）;第10天血清HBVDNA水平分别为4.38±0.22 lgcopies/ml和6.56±0.16lgcopies/ml（P=0.008）;第15天为4.41±0.88lgcopies/ml和5.69±0.04lgcopies/m（l P=0.177）;第25天为4.48±0.04lgcopies/ml和6.44±0.16lgcopies/ml（P=0.004）;第40天为3.66±0.45lgcopies/ml和5.20±0.28lgcopies/ml（P=0.055）;两组血清HBV DNA持续存在,在转染后第40天仍为阳性。肝组织HBcAg持续阳性,在转染后第4天、15天和40天均呈高表达,但CXCR3基因敲除小鼠肝组织HBcAg表达较低。结论我们成功建立了CXCR3基因敲除小鼠慢性HBV复制模型,可用于进一步研究CXCR3基因及其配体与HBV感染的关系。

英文摘要：

Objective To establish a HBV infection model of CXCR3 knocked-out mice.Methods After CXCR3 knocked-out,nine of them and nine wild-type C57BL/6 mice were injected hydrodynamically ten micrograms of pAAV/HBV1.2 DNA into the tail veins.Then,the mice were regularly bled to monitor the serum levels of HBsAg,HbeAg and HBV DNA.The HBcAg in the livers from injected mice were detected by immunohistochemistry.Results All the bred CXCR3 knocked-out mice were homozygous.The serum levels of HBsAg from the CXCR3 knocked-out mice and the wild type C57BL/6 were 1134.69±244.42 and 1759.63±881.20（P=0.096） at the first day after the injection of the pAAVHBV1.2 plasmids;5305.29±1395.06 and 7493.29±658.63（P=0.003） at the fourth day,1615.04±1187.16 and 1536.19±1046.02（P=0.905） at the fifteenth day,and 229.45±79.27 and 228.19±295.02（P=0.996） at fortieth day,respectively;the serum levels of HBeAg from them were 6.65±1.50 and 20.61±4.03（P=0.000） at the first day,6.33±1.61 and 9.79±2.31（P=0.007） at the fourth day,3.52±1.97 and 2.85±0.74（P=0.425） at the fifteenth day,and 1.28±0.06 and 1.90±1.01（P=0.431）at fortieth day,respectively and the serum levels of HBV DNA from them were 4.38±0.22 lgcopies/ml and 6.56±0.16 lgcopies/ml（P=0.008） at day10,4.41±0.88 lg copies/ml and 5.69±0.04 lg copies/ml（P=0.177） at day15,4.48±0.04 lgcopies/ml and 6.44±0.16 lgcopies/m（P=0.004） at day25,and 3.66±0.45 lgcopies/ml and 5.20±0.28 lg copies/ml（P=0.055） at day40,respectively;HbsAg,HbeAg and HBV DNA in CXCR3 knocked-out mice were continuously positive untill the day 40 after the injection of the pAAV/HBV1.2 DNA;Both cytoplasmic and nuclear HBcAg were detected in the livers of the CXCR3 knocked-out mice at the day 4,15,40 after the infection.The positive serumHBsAg,HbeAg and HBV DNA in CXCR3 knocked-out mice were similar to those in the wild type C57BL/6 mice.Conclusion We had successfully established a HBV infection model in CXCR3 knocked-out mouse,which might be helpful way to investigate