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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 investigate the anti-duck hepatitis B virus (DHBV) activity of acellular Corynebacterium parvum nano-preparation (NCPP). Methods The positive serum of duck hepatitis B virus was injected into the tibial vein of duck to establish the animal model of hepatitis B virus. The Corynebacterium parvum nanoflora was divided into three groups (0.9 mg · qod-1 per feather), medium (0.3 mg · qod-1 per feather) and low (0.1 mg · qod- 7 days after modeling intramuscular injection, a total of 6 times; positive control lamivudine intragastric administration (50 mg · kg-1 · d-1), a total of 11 times; also set avian interferon α control, oral drip (1 000 u · qod-1 per feather) for a total of 6 times. The levels of anti-duck hepatitis B virus-DNA in the duck serum before 3 d, 6 d, 12 d, and 3 d after drug withdrawal were detected by dot blot hybridization. The duck liver organization. Results Serum anti-duck hepatitis B virus-DNA levels in each dose group and lamivudine group at each blood sampling time point were significantly lower than those in the corresponding model group (P <0.001) ; The inhibitory rates of medium and low dose groups were above 60%, higher than that of lamivudine (58%) after 3 days of drug withdrawal; the effect of avian interferon-α on serum anti-duck hepatitis B virus No significant inhibition of the load. The pathological results of liver showed that the changes of hepatocyte edema, steatosis and inflammatory cell infiltration in each dose group of Corynebacterium parvum were improved to some extent compared with the model group. The low-dose group of Corynebacterium parvum nano-preparation Inflammatory infiltration improved significantly. Conclusion The cell-free Corynebacterium parvum nanoflora showed obvious inhibitory effect on duck hepatitis B virus and was beneficial to improve inflammatory infiltration status.