树鼩感染丁型肝炎病毒的实验研究

The infection of hepatitis D virus in adult tupaia

作者以树为对象、建立丁型肝炎病毒（ＨＤＶ）／乙型肝炎病毒（ＨＢＶ）实验感染动物模型，为丁型肝炎发病机理和药物筛选提供研究基础。对人工饲养的２０只健康成年树 接种ＨＢＶＤＮＡ阳性血清后ＨＢｓＡｇ的转阳率为７５％（１５只）；分别以同时感染（１３只）和重叠感染（９只）两种方式接种ＨＢＶＤＮＡ和ＨＤＶＲＮＡ阳性血清后，各有８只和６只树 的血清乙肝表面抗原（ＨＢｓＡｇ）、丁肝抗原（ＨＤＡｇ）和丁肝抗体（抗ＨＤ）相继转阳，部分血清或肝内检出ＨＤＶＲＮＡ，以ＨＤＶ／ＨＢＶ阳性树 血清在树 间进行传代感染，可见第二代４只中３只、第三代５只中４只树 的血清ＨＢｓＡｇ、ＨＤＡｇ和抗ＨＤＶ相继转阳，２只第三代感染树 血清中检出ＨＤＶＲＮＡ，肝内检出ＨＢｓＡｇ和ＨＤＡｇ阳性；连续观察１６～１９个月，经重叠感染成功的４只树 血清ＨＢｓＡｇ持续阳性，２只ＨＤＡｇ和抗ＨＤ交替出现，１只抗ＨＤ持续阳性，提示可发展成慢性ＨＤＶ感染；感染ＨＤＶ的树 血清ＡＴＬ升高，肝组织有类似肝炎样病理变化，与ＨＤＶ在黑猩猩体内感染结果类似，提示树 可作为ＨＤＶ感染的动物模型。

A new animal model of HDV/HBV infection in adult tupaia (tree shrews) was established to study its pathogenesis and treattment of hepatitis D. In 20 artificially fed adult tupaiae, the positive rate of serum HBsAg was 75% (15/20)after inoculation of human HBV DNA positive serum. After inoculation with positive human serum HBV DNA and positive HDV RNA by way of coinfection and superinfection, serum HBsAg.HDAg and anti-HD were positive one after another in 8 out of 13 tupaiae of the coinfection group and in 6 out of 9 tupaiae of the superinfection group.In some of them HDV RNA was positive in serum or in liver tissue.Transmission of HDV/HBV infection among tupaiae was successful. In group I,animals were inoculated with human HDV/HBV positive serum. In GroupⅡand Ⅲ,animals were inoculated with tupaia HDV/HBV positive serum of the Group I and Ⅱ respectively. Serum HBsAg, HDAg and anti-HD became positive one after another in 3 out of 4 tupaiae of the Group Ⅱand 4 out 5 tupaiae of the group Ⅲ. In 2 animals of the Group Ⅲ,serum HDV RNA was positive and HBsAg and HDAg were detected in the liver tissue. Serum HBsAg was persistantly positive for 16￣19 months in the superinfection group. In 2 of them, serum HDAg and anti-HD were alternatively positive and in one of them serum anti-HD was positive persistantly indicating that HDV infection may persist and transform into chronic HDV infection. In the HDV infected tupaiae, there were elevated serum ALT and hepatitis-like pathological changes in the liver tissue which were similar to those in the chimpanzee. We conclude that tupaia may be used as an experimental model of hepatitis D.