树鼩传代感染HDV后肝脏内抗原表达及病理变化

目的观察树（Ｔｕｐａｌａ）经人工传代感染ＨＤＶ后肝内ＨＤＡｇ表达及病理变化方法驯养的野生Ｔｕｐａｉａ第一代接种人ＨＤＶ阳性血清，第二、三代分别接种第一、二代感染ＨＤＶ成功的Ｔｕｐｓｉａ血清０，４ｍＬ／只，感染前３ｗｋ所有Ｔｕｐａｉａ均接种了人ＨＢＶ阳性血清０．４ｍＬ／只，接种ＨＤＶ前及以后每周取血及肝脏标本一次，连续６ｗｋ肝组织石蜡包埋，分别采用ＨＥ及ＳＰ法染色观察病理变化及抗原表达，原位杂交法观察ＨＤＶＲＮＡ．结果第一代１／１只，第二代３／４只，第三代５／５／ｑＴｕｐａｉａ于感染ＨＤＶ阳性血清２ｗｋ后肝内均可检出ＨＤＡｇ，持续至ｗｋ６观察结果时，ＨＤＡｇ定位于肝细胞核和浆内，少数呈膜型，阳性肝细胞呈片状分布，亦可散在表达于单个肝细胞内，ＨＤＶＲＮＡ主要在肝细胞核内表达肝组织呈病毒性肝炎样病理变化，如变性点灶状坏死及汇管区炎细胞浸润．结论Ｔｕｐｓｉａ传代感染ＨＤＶ肝脏病理变化及ＨＤＡｇ表达与在黑猩猩中十分类似，提示Ｔｕｐａｔａ可作为感染ＨＤＶ实验动物

Expression of intrahepatic HDAg and pathological changes following serial passages of HDV infection in tupaiae

ATM To observe the intrahepatic HDAg and pathologicalchanges following artificial serial passages of HDV infection in tupaiae.METHODS All of the experimental animals used in thisstudy are wild tupaiae. In the serial Passages, the first tupaia was inoculated with human HDV positive serum, 4 tupaiae of the second passage with 0.4 mL of the serum ofthe first passage, and the 5 tupaiae of the third with0 .4 mL of the 2nd passage. All of the 9 tupaiae were inoculated with human HBV positive serum 3 -- 5 weeks beforeHDV injection. Blood samples and liver tissue specimenswere collected once a week for at least 6 weeks.Patho-logical changes (H. E. stain), intrahepatic HDAg (S--Pmethod) and HDV RNA (hybridization in situ ) were studied.RESULTS Surum HDAg was detectable in 3/ 4 of the 2ndPassage, in 4/ 5 of the 3rd, and HDV RNA was detectablein 4/ 6. HDAg was expressed in the liver tissue in 3/ 4 ofthe 2nd passage and in all the 5 of the 3rd Passage, whichwas in nucleus type, plasma type, membrane type andmixed type. It appeared from the 2nd week and lastedmore than 6 weeks. HDV RNA was expressed mainly in thenucleus of the hepatocytes. There were viral hepatitis--likepatholOgical changes in the liver tissue, such as degeneration, spot or local necrosis and inflammatory infiltrationin the portal space.CONCLUSION Pathological changes and HDAg expressionin the liver tissue were quite similar to those in chimpanee. Tupaia may be used as an ideal animal model ofHDV infection.