类鼻疽杆菌慢性感染BALB/c小鼠模型的建立

目的 建立类鼻疽杆菌(Burkholderia pseudomallei)慢性感染BALB/c小鼠模型并评价其稳定性.方法 采用0.01 mL洗涤后的高、中、低剂量的类鼻疽杆菌液(菌量分别为3.3×104、3.3×103、3.3×102 CFU)滴鼻感染BALB/c小鼠,密切监测42 d,记录小鼠的生存率,探索合适的攻毒剂量.在低剂量细菌(3.3×102 CFU)感染小鼠后21、28、35、42 d,计数小鼠血液、肝脏、脾脏和肺脏的细菌定植量,ELISA检测血清炎性因子TNF-α、IFN-γ的表达和血清类鼻疽杆菌特异性IgG抗体滴度,观察肝脏、脾脏和肺脏等主要器官的病理学改变,评价动物模型的稳定性.结果 低剂量类鼻疽杆菌滴鼻感染BALB/c小鼠后,小鼠42 d生存率为60％.期间小鼠体质量呈下降趋势,血液、肝脏、脾脏和肺脏均有细菌定植,并出现大量炎性细胞浸润、多灶性坏死和脓肿等病理改变;类鼻疽杆菌血清中特异性IgG抗体滴度从感染后21 d起持续增高;实验组小鼠血清炎性因子TNF-α和IFN-γ表达明显高于对照组(P＜0.05).结论 成功建立了稳定的类鼻疽杆菌慢性感染BALB/c小鼠模型.

Establishment of a BALB/c mouse model of melioidosis induced by chronic Burkholderia pseudomallei infection

Objective To establish a BALB/c mouse model of melioidosis induced by chronicBurkholderia pseudomallei (B.pseudomallei) infection.Methods BALB/c mice were challenged with different doses (3.3 × 104,3.3 × 103,and 3.3 × 102 CFU) of B.pseudomallei by intranasal instillation.The mice were monitored daily for 42 d to record their survival rate and body weight changes.On days 21,28,35 and 42 following the infection,the bacterial loads in the blood and organs and the serum levels of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ) and specific anti-B.pseudomallei IgG were detected,and the pathological changes in the liver,pancreas and lungs of the mice were assessed using HE staining.FeSults Intranasal challenge with a low dose (3.3 × 102 CFU) of B.pseudomallei resulted in a survival rate of 60％ in the mice on day 42.Chronic B.pseudomallei infection of the mice caused progressive body weight loss and induced obvious pathologies (inflammatory cell infiltration,multiple focal necrosis and abscess) in the liver,pancreas and lungs,where B.pseudomallei colonization was detected.The serum titer of specific B.pseudomallei IgG began to increase continuously from day 21 after the challenge,and the serum levels of TNF-α and IFN-γ were significantly higher in the infected mice than in the control mice.Concltusion We have successfully established a model of chronic B.pseudomallei infection in BALB/c mice.