Heuer Josef G, Bailey Dianna L, Sharma Ganesh R, Zhang Tonghai, Ding Chunjin, Ford Amy, Stephens Eddie J, Holmes Kimberly C, Grubbs Renee L, Fynboe Kelly A, Chen Yun-Fei, Jakubowski Joseph A
Biotechnology Discovery Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
J Surg Res. 2004 Oct;121(2):178-86. doi: 10.1016/j.jss.2004.04.018.
Standard rat cecal ligation and puncture (CLP) results in only transient hyperglycemia, making an examination of the effects of glucoregulatory agents, such as insulin, on the morbidity and mortality of CLP problematic. Accordingly, we sought to develop a model of rat CLP with prolonged hyperglycemia through continuous infusion of total parenteral nutrition (TPN) post CLP.
Polyethylene catheters were implanted into the femoral vein of female Sprague Dawley rats (245-265 g) which were subsequently subjected to CLP. TPN was initiated at different intervals following CLP, and mortality, bacteremia, blood glucose, hormonal, and inflammatory responses were monitored.
Without TPN, CLP resulted in significantly lower blood glucose at 22 h post CLP. In contrast, CLP rats receiving TPN exhibited significant prolonged hyperglycemia that was responsive to insulin treatment. Mortality and hyperglycemia tended to increase with puncture size in CLP TPN rats, with early initiation of TPN leading to poorer outcome. There were time-dependent differences in bacteremia and mortality based on time of TPN initiation. Levels of insulin, leptin, and glucagon were significantly elevated in CLP TPN rats, as were many inflammatory markers. Organ damage was evident as early as 12 h post CLP and blood cell kinetics indicated significantly depressed neutrophil and lymphocyte counts.
Our results indicate that addition of TPN to CLP provides a clinically relevant animal model of critical illness with associated hyperglycemia that may provide utility for the testing of glucoregulatory and other therapeutic modalities.
标准的大鼠盲肠结扎穿刺术（CLP）仅导致短暂的高血糖，这使得研究胰岛素等血糖调节药物对CLP发病率和死亡率的影响存在问题。因此，我们试图通过在CLP后持续输注全胃肠外营养（TPN）来建立一种具有持续性高血糖的大鼠CLP模型。
将聚乙烯导管植入雌性Sprague Dawley大鼠（245 - 265克）的股静脉，随后对其进行CLP。在CLP后的不同时间间隔开始给予TPN，并监测死亡率、菌血症、血糖、激素和炎症反应。
未给予TPN时，CLP导致CLP后22小时血糖显著降低。相比之下，接受TPN的CLP大鼠表现出显著延长的高血糖，且对胰岛素治疗有反应。CLP TPN大鼠的死亡率和高血糖倾向于随穿刺大小增加，早期开始给予TPN导致预后较差。基于TPN开始时间，菌血症和死亡率存在时间依赖性差异。CLP TPN大鼠的胰岛素、瘦素和胰高血糖素水平显著升高，许多炎症标志物也是如此。早在CLP后12小时器官损伤就很明显，血细胞动力学表明中性粒细胞和淋巴细胞计数显著降低。
我们的结果表明，在CLP基础上加用TPN可提供一种具有临床相关性的伴有高血糖的危重病动物模型，这可能有助于测试血糖调节及其他治疗方式。
