肺炎克雷伯菌肝脓肿小鼠模型的建立

    Establishment of liver abscess model of Klebsiella pneumoniae in mice

    • 摘要: 为构建稳定可靠的肺炎克雷伯菌肝脓肿(KPLA)动物模型,选取18 g左右健康ICR小鼠,以高毒力动物源肺炎克雷伯菌临床分离株KP001为造模菌株,分别从接种方式(灌胃、滴鼻和腹腔注射,接种菌数为1×107 CFU)和接种剂量进行摸索,并对造模成功小鼠的血清样品进行谷丙转氨酶、谷草转氨酶、碱性磷酸酶、γ-谷氨酰转移酶、白蛋白、乳酸脱氢酶、总胆红素等生化指标的测定。结果表明:灌胃小鼠存活率100%,但肝脏未出现脓肿;滴鼻小鼠死亡率100%,肺脏病变明显,40%死亡小鼠肝脏出现脓肿;腹腔注射1×106 CFU细菌后,小鼠存活率为75%以上,且存活小鼠肝脏均出现脓肿,成模率100%。病理切片显示造模成功小鼠肝细胞排列紊乱,中央静脉周围有大量炎性细胞浸润。生化指标检测显示,与对照小鼠相比,造模成功小鼠的血清样品中γ-谷氨酰转移酶极显著升高(P<0.01),碱性磷酸酶极显著下降(P<0.01),谷丙转氨酶、白蛋白显著下降(P<0.05)。结果表明,通过腹腔注射方式,接种1×106 CFU KP001菌株后可成功构建KPLA小鼠模型,γ-谷氨酰转移酶和碱性磷酸酶等生化指标可用于评估模型建立效果。

       

      Abstract: To construct a stable and reliable animal model of Klebsiella pneumoniae liver abscess(KPLA), healthy ICR mice weighing around 18 g were selected, and a highly virulent clinical isolate of Klebsiella pneumoniae, strain KP001, was used as the modeling strain. The inoculation methods(gavage, intranasal, and intraperitoneal injection)and doses were explored, and the serum samples from successfully modeled mice were tested for biochemical indicators such as alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), gamma-glutamyltransferase(GGT), albumin, lactate dehydrogenase(LDH), and total bilirubin. The results showed that mice gavaged had a survival rate of 100%, but no abscesses in the liver; mice intranasally inoculated had a mortality rate of 100%, with obvious lung lesions, and 40% of the dead mice developed liver abscesses; after intraperitoneal injection with 1×106 CFU of bacteria, the survival rate of mice was 87.5%, and all surviving mice had abscesses in the liver, with a modeling success rate of 100%. Pathological sections showed that the liver cells of successfully modeled mice were disordered, with a large number of inflammatory cells infiltrating around the central vein. Biochemical indicator tests showed that compared with the control mice, the serum samples of successfully modeled mice had a significantly increased level of gamma-glutamyltransferase(p<0.001), a significantly decreased level of alkaline phosphatase(p<0.01), alanine aminotransferase(p<0.05)and albumin(p<0.05). The results indicated that by intraperitoneal injection with 1×106 CFU of KP001 strain, a KPLA mouse model could be successfully established; biochemical indicators such as gamma-glutamyltransferase and alkaline phosphatase can be used to evaluate the effectiveness of model establishment. This study is of great significance for the study of the pathogenesis of KPLA and the evaluation of therapeutic effects.

       

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