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[目的]建立小鼠急性乙型肝炎病毒(HBV)感染的动物模型,观察小干扰RNA(si RNA)在体内对HBV复制和表达的影响.[方法]通过尾静脉快速、高负荷注射含1.5倍的HBV真核表达质粒(pHBV1.5).注射后第6天,MEIA检测血清HBsAg、HBeAg的水平;RT-PCR检测肝组织HBV prec/c mRNA转录的水平.同时设立pcDNA3.1正常对照组和PBS空白对照组.[结果]pHBV1.5注射组小鼠血清HBsAg、HBeAg为阳性,且肝组织表达HBeAg;而pcDNA3.1和PBS对照组未能检测到HBsAg、HBeAg的表达.[结论]成功地建立了急性HBV感染的BALB/C小鼠动物模型,在一定程度上克服了由于HBV宿主范围极窄给人们研究带来的极大限制. 相似文献
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流体动力学法乙型肝炎病毒感染动物模型的建立 总被引:4,自引:0,他引:4
目的:建立一种简便、有效、稳定的乙型肝炎病毒(HBV)感染的动物模型,观察该模型动物体内不同时间点各种HBV标志物的表达情况.方法:以流体动力学法尾静脉注射BALB/c 小鼠pcDNA3.1-HBV,1 wk内检测各种HBV 标志物,时间分辨免疫荧光分析法(IFMA)检测血清中HBsAg,HBeAg,抗HBs,抗HBe,抗 HBc,荧光定量PCR法(FQ-PCR)检测血清HBV DNA,免疫组织化学法检测肝组织HBsAg和 HBcAg.结果:成功建立一种急性HBV感染动物模型, 第1天血清中HBsAg表达达高峰,后逐渐降低, HBeAg表达量少,分别在第4、5、7天检测到抗HBc,抗HBe,抗HBs,d1 HBV DNA滴度亦达高峰,后渐下降,免疫组织化学示HBsAg呈胞质内弥漫性分布,HBcAg亦主要为胞质型分布.结论:以流体动力学法建立的HBV模型是一种新型有效的HBV感染动物模型,能稳定较高水平表达大部分HBV标志物. 相似文献
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鸭乙型肝炎病毒感染模型的研究进展 总被引:5,自引:0,他引:5
HBV和DHBV均为嗜肝DNA病毒,它们都有相似的基因组和病毒结构特征,以及通过RNA逆转录复制的特性。DHBV感染鸭模型是研究HBV基因突变、细胞表面病毒受体、病毒清除机制以及筛选新的抗病毒药物的合适的动物模型。文章就鸭乙型肝炎病毒感染模型的研究情况作一简要综述。 相似文献
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乙型肝炎病毒感染是全球范围内影响人类健康的重要问题,目前人们对HBV及其所致疾?膊 病有了相当深入的认识.但由于缺乏合适的动物模型,乙型肝炎病毒的生物学研究和治疗进展缓慢.小鼠作为一种实验室常用的动物,遗传免疫背景清楚明确,已经成为人们研究乙肝的重要工具.本文简要综述了小鼠模型在乙型肝炎研究中的进展. 相似文献
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目的:建立日本血吸虫重叠 HBV 感染小鼠模型,观察其生物学表现。方法日本血吸虫尾蚴感染6~8周龄雌性 BALB/cJ 小鼠,8周后,通过高压尾静脉注射 B 基因型 HBV 可复制性克隆,分别在注射后第3、7天,检测血清HBV DNA、HBsAg、HBeAg、ALT、透明质酸(HA)水平;检测 HBcAg 在肝细胞内表达情况和虫卵肉芽肿形成情况。比较重叠感染相关生物学指标和单独感染组的不同。结果重叠感染组小鼠肝组织内可见 HBcAg 在虫卵肉芽肿周围肝细胞内表达;可以正常分泌 HBsAg 和 HBeAg 以及子代病毒;其血清 ALT 水平低于 HBV 感染组,高于血吸虫感染组;HA 含量相对明显升高。结论成功建立了日本血吸虫重叠 HBV 感染小鼠模型,为后续研究此类重叠感染提供了良好的小动物实验平台。 相似文献
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鸭乙型肝炎肝纤维化模型的初步研究 总被引:7,自引:0,他引:7
目的:研制乙型肝炎纤维化的动物模型,方法:采用1d龄樱桃谷鸭,随机分为正常组,鸭乙型肝炎病毒(DHBV)造模组及CCl4造模组,分别于60、100及112d随机抽样观察两造模组鸭肝组织病变化,于100d检测3组动物肝组织DHBV、DNA、肝功能和肝纤维化的指标。结果 CCl4造模组脂肪变性明显,肝细胞水样变性伴中等炎怀细胞浸润,纤维组织增生明显,DHBV造模模组以水样变性为主,可直窦消失或肝窦扩张 相似文献
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目的研制乙型肝炎肝纤维化的动物模型.方法采用1d龄樱桃谷鸭,随机分为正常组、鸭乙型肝炎病毒(DHBV)造模组及CCl4造模组,分别于60、100及112d随机抽样观察两造模组鸭肝组织病理变化,于100d检测3组动物肝组织DHBV、DNA、肝功能和肝纤维化指标.结果CCl4造模组脂肪变性明显,肝细胞水样变性伴中等炎性细胞浸润,纤维组织增生明显;DHBV造模组以水样变性为主,可见肝窦消失或肝窦扩张瘀血,脂肪变性以小脂滴为主,肝细胞坏死程度较轻,但炎性细胞浸润明显,且以淋巴细胞多见,纤维增生形成时间略长,60d尚未见纤维增生,80d时汇管区纤维组织中度增生,100d和112d时纤维组织明显增生,有的形成假小叶,其纤维化形成率与CCl4组(90%)接近(100d为60.7%,112d为87.5%).肝组织DHBVDNA检测结果,DHBV造模组水平较高,其肝功能ALT正常,白蛋白明显降低,球蛋白显著升高,肝纤维化指标如HA、PCⅢ和肝组织Hyp均明显上升.结论采用DHBV阳性血清反复攻击樱桃谷鸭112d以上,可复制形成率较高的鸭乙型肝炎肝纤维化模型. 相似文献
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迄今为止尚无可靠的HBV体外感染系统和实用的动物模型,严重阻碍了其相关研究。因此建立生物学背景清晰、易于获取、经济适用的小动物模型尤为重要。目前有关HBV感染模型的研究大多集中在小鼠方面,并已取得了很大进展。本文就近年来有关HBV复制感染的小鼠模型研究成果进行综述。 相似文献
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乙型肝炎病毒感染的综合性预防 总被引:12,自引:1,他引:12
吴君 《世界华人消化杂志》2006,14(12):1135-1138
乙型肝炎病毒(HBV)疫苗接种实行计划免疫以来,母婴垂直传播得到了有效的控制.但高危人群的性传播、医源性传播、静脉注射毒品等水平传播增多,还有农村地区HBV疫苗接种率低、接种失败、献血员漏检、HBV变异株增多,HBeAg(-)慢性乙型肝炎比例增多存在HBV隐匿性感染等.因此,需要实施多环节综合性的预防策略来有效的阻止HBV的感染.他们分别是:推行大面积的HBV免疫计划确实实施对新生儿(包括农村地区)、高危成年人群及未接种人群的HBV疫苗的接种和接种后监测管理;乙肝免疫球蛋白(HBIG)被动免疫与HBV疫苗主动免疫联合阻断包括宫内感染在内的母婴垂直传播和意外暴露HBV后预防;重视对血制品、器官组织和捐献者的病毒核酸检测;加强对医务人员的医疗行为规范、医疗器械的消毒和HBV防治知识的宣传教育等等. 相似文献
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Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection 总被引:12,自引:0,他引:12
BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma. 相似文献
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Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients 总被引:4,自引:0,他引:4
Masato Komori Nobukazu Yuki Takayuki Nagaoka Masatoshi Yamashiro Kiyoshi Mochizuki Akira Kaneko Keiji Yamamoto Kazumasa Hikiji Michio Kato 《Journal of hepatology》2001,35(6):15-804
BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance. 相似文献
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In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as thepresence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays.Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this ... 相似文献
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Hao Wang Min Wang Jieting Huang Ru Xu Qiao Liao Zhengang Shan Yourong Zheng Xia Rong Xi Tang Tingting Li Wenjing Wang Chengyao Li Yongshui Fu 《Journal of viral hepatitis》2020,27(9):915-921
The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty‐seven hepatitis B surface antigen (HBsAg)‐positive/HBV DNA‐positive blood donors served as control group for comparison. Occult HBV‐related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection‐related mutations, a conservative full‐gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection‐related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion. 相似文献
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Nicola Coppola Lorenzo Onorato Mariantonietta Pisaturo Margherita Macera Caterina Sagnelli Salvatore Martini Evangelista Sagnelli 《World journal of gastroenterology : WJG》2015,21(42):11931-11940
The development of sensitive assays to detect small amounts of hepatitis B virus(HBV) DNA has favored the identification of occult hepatitis B infection(OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV(HBs Ag) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody(antiHBc) in serum of HBs Ag-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C(CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma(HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC. 相似文献