克雷伯杆菌肺炎老龄大鼠多器官损伤模型的建立

A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats

目的建立细菌性老龄大鼠多器官损伤模型。方法将大鼠随机分为老龄对照组、老龄模型组和青年对照组、青年模型组。采用气管插管法注入肺炎克雷伯杆菌引起肺部炎症，根据脏器有关生化指标变化、病理学改变及动物死亡率等情况评价该模型。结果青年模型组和老龄模型组制模24h后大鼠死亡率分别为33．3％（5／15）和60．0％（15／25）。与同龄对照组比较，青年模型组和老龄模型组外周血白细胞计数和中性粒细胞比例明显增高（P均〈0．01）；肺、心、肝功能障碍发生率为60％～100％；肺动脉血氧分压（PaO2）明显下降，动脉血二氧化碳分压（PaCO2）显著上升（P〈0．05或P〈0．01）；血清肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）和丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）明显增高（P〈0．05或．P〈0．01）；脏器组织学发生了明显的病理学改变。与青年模型组比较，老龄模型组肺PaO2明显下降、PaCO2显著上升；血清CK、CK-MB、LDH和ALT、AST明显增高（P〈0．05或P〈0．01）；肺、心、小肠病理损伤评分显著增高（P均〈0．05），肝、肾亦有增高趋势。结论成功地制备了细菌性老龄大鼠多器官损伤模型，符合老年“肺启动”机制多器官功能障碍综合征（MODS）特征，该模型制备简便，成功率高。脏器损伤重、死亡率高为老龄大鼠多器官损伤的特点。

Objective To reproduce a model of bacterial multiple organ injury （MOI） in aged rats. Methods Male Sprague-Dawley （SD） rats were used. The young rats were divided into young control group （YCG, n = 10） and young model group （YMG, n = 15）, and the elderly, aged control group （ACG, n = 10） and aged mode/group （AMG, n= 25）. The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality. Results Between YMG and AMG, the mortality rates were 33.33% （5/15） and 60. 00% （15/25）, respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell （WBC） counts in peripheral blood increased significantly in YMG and AMG groups （all P〈0.01）, the rates of dysfunction of the lungs, the heart and the liver, were 60%- 100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide （PaCO2, P〈0. 01）, and a decrease in the arterial partial pressure of oxygen （PaO2, P〈0. 05 or P〈0. 01）. Myocardial dysfunction was shown by a the sharp increase in creatine kinase （CK）, ereatine kinase isoenzyme MB （CK-MB） and lactate dehydrogenase （LDH）, and that of the liver by changes in alanine aminotransferase （ALT） and aspartate aminotransferase （AST, P〈0.05 or P〈0.01）. The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO2 in AMG dropped significantly, PaCO2 increased, CK, CK-MB, LDH, ALT and AST also increased significantly （P〈0. 05 or P〈0. 01）. The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group （all P〈0.05）, and the same was trend in the liver and the kidney. Conclusion The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome （MODS） which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.