重组小鼠β防御素3体内抗甲型流感病毒H1N1作用

Anti-influenza A Virus H1N1 Activity of Recombinant Mouse Beta Defensin 3 in Vivo

关键词:  防御素  重组蛋白  抗病毒活性  甲型流感病毒

Key words:  defensin  recombinant protein  anti-viral activity  influenza A virus

摘要:

目的 观察重组小鼠β防御素3(rMBD3)对甲型流感病毒感染小鼠的保护作用。方法 以10 mg·kg^-1·d^-1rMBD3腹腔注射3月，观察小鼠的一般状态，以及对主要脏器的影响。BALB/c小鼠，♀，分为正常对照组、模型对照组、rMBD3高剂量组(10 mg·kg^-1·d^-1)、rMBD3低剂量组(5 mg·kg^-1·d^-1)和利巴韦林组(100 mg·kg^-1·d^-1)。采用流感病毒液滴鼻感染建立甲型流感病毒H1N1感染小鼠模型，感染病毒12 h后分别腹腔注射给药。每日观察小鼠一般情况和死亡情况。于攻毒第3天检测肺泡灌洗液流感病毒滴度、血清γ干扰素含量、肺指数和肺组织病理变化。结果 小鼠腹腔注射10 mg·kg^-1·d^-1 rMBD3 3月，未发现明显异常反应或死亡，各重要脏器的未见明显病理改变。rMBD3各剂量组肺泡灌洗液中的病毒滴度、肺指数抑制率均降低，肺组织病理改变减少。结论 rMBD3对小鼠无明显毒性作用，在体内具有抗流感病毒、保护流感小鼠的活性。

Abstract:

OBJECTIVE To explore the protective activity of recombinant mouse beta defensing 3(rMBD3) in influenza A virus infected mice. METHODS Mice were intraperitoneal injected with 10 mg·kg^-1·d^-1 rMBD3. Three months later the general condition of mice were observed. BALB/c mice, ♀, were divided into five groups: normal control group, model control group, rMBD3 high dose group(10 mg·kg^-1·d^-1), rMBD3 low dose group(5 mg·kg^-1·d^-1) and ribavirin (100 mg·kg^-1·d^-1) group. The H1N1 infected model was established by influenza virus nasal drip. The mice were given drugs by intraperitoneal injection after infected for 12 h. The weight and survival of mice were surveyed daily. On the 3rd day, the virus titer in bronchoalveolar lavage fluids, lung index and the histological patterns of major organs were observed. The serum interferon-γ was determined by ELISA kit. RESULTS There was no abnormal reaction or death of the mice after injected 10 mg·kg^-1·d^-1 rMBD3 for 3 months. Obvious pathological changes of each important organs were not found. Each dose group of rMBD3 reduced the influenza virus titer in bronchoalveolar lavage fluids, lung index inhibition and lung tissue pathological changes. CONCLUSION rMBD3 shows no obvious toxic effects in mice, and has the activity of anti-influenza virus in vivo and protection of the mice with influenza.