无细胞短棒状杆菌纳米制剂抗鸭乙型肝炎病毒作用研究  

Anti-Duck Hepatistic B Virus Effects of Non-Cell Corynebacterium parvum Preparation Prepared by Nano-technology

作　　者：王玉梅[1] 周亚伟[2] 李守悌[1] 高尚先[1] 

机构地区：[1]中国食品药品检定研究院,卫生部生物技术产品检定方法及其标准化重点实验室,北京100050 [2]北京大学世佳研究中心,北京100084

出　　处：《中国药学杂志》2014年第19期1687-1691,共5页Chinese Pharmaceutical Journal

摘　　要：目的探讨无细胞短棒状杆菌纳米制剂(NCPP)抗鸭乙型肝炎病毒(duck hepatitis B virus,DHBV)的活性。方法麻鸭胫静脉注射抗鸭乙型肝炎病毒阳性血清,建立乙型病毒性肝炎动物模型。无细胞短棒状杆菌纳米制剂给药分高(每羽0.9mg·qod-1)、中(每羽0.3 mg·qod-1)、低(每羽0.1 mg·qod-1)3个剂量组,造模后7 d肌肉注射,共6次;阳性对照用拉米夫定灌胃(50 mg·kg-1·d-1),共11次;同时设禽α-干扰素对照,口腔滴注(每羽1 000 u·qod-1),共6次。分别以斑点杂交法检测给药前,第6天、第12天,停药后第3 d鸭血清中抗鸭乙型肝炎病毒-DNA的含量,以病理学检测停药3 d后的鸭肝组织。结果无细胞短棒状杆菌纳米制剂各剂量组与拉米夫定组在各采血时间点的血清抗鸭乙型肝炎病毒-DNA水平与相应的模型组相比均有显著性下降(P<0.001);中、低剂量组的抑制率均在60%以上,高于拉米夫定在停药3 d后的抑制率(58%);禽α-干扰素组对血清中抗鸭乙型肝炎病毒的载量无明显抑制。肝脏病理结果显示,无细胞短棒状杆菌纳米制剂各剂量组肝细胞水肿、脂肪变性及炎性细胞浸润等变化均较模型组有不同程度的改善,以无细胞短棒状杆菌纳米制剂小剂量组对炎性浸润的改善较显著。结论无细胞短棒状杆菌纳米制剂表现出对鸭乙型肝炎病毒明显的抑制作用,且有利于改善炎症浸润状态。OBJECTIVE To study the anti-duck hepatistic B virus （DHBV） effects of non-cell Corynebacterium parvum preparation （NCPP） prepared by nanotechnology. METHODS Patridge ducks were injected with DHBV positive sera by vena cruralis to establish DHBV infected model. NCPP was divided into 3 groups： high-dose group （0.9 mg· qod-1 per duck） , mid- dle-dose group（0.3 mg ·qod-1 per duck） and low-dose group （0. 1 mg· qod-1 per duck）. Seven days after modeling, NCPP was given intramuscularly for a total of 6 times; the positive control drug, lamivudine, was administered intragastrically at 50 mg ·kg-1 · d-1 for a total of 11 times. The ducks in another control group were given orally poultry a-interferon （ 1 000 u · qod-1 ） for a total of 6 times. DHBV levels in the duck serum were detected by dot blot hybridization before administration, at 6, 12 d after administration and 3 d after discontinuation, respectively. The pathology of the liver tissues of the ducks in each group was analyzed after discontinuation. RESULTS The DHBV-DNA levels in the duck serum of each dose group of NCPP and lami- vudine at each blood sampling time point were significantly decreased compared with the corresponding model group （P 〈 0. 001 ） ; the inhibition rates of NCPP medium-dose group and low-dose group at each time point were more than 60% , which were higher than that of lamivudine group （58%） at 3 d after discontinuation. No significant inhibitory effects on the load of ser- um DHBV were found in poultry c--interferon group. Pathological analysis results showed that hepatocyte edema, fatty degenera- tion and inflammatory cell infiltration in each NCPP group were improved significantly compared with model group, and low dose NCPP improved the inflammatory infiltration more significantly. CONCLUSION NCPP shows significant effects of anti-DHBV and improvement of inflammatory infiltration.

关 键 词：短小棒状杆菌 鸭乙型肝炎病毒 纳米技术 斑点杂交 肝组织病理学 

分 类 号：Q81[生物学—生物工程]