Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing 210002, Jiangsu Province, China.
Center for Immunology and Infectious Diseases, Biosciences Division, SRI International, Harrisonburg, VA 22802, USA.
Sci Rep. 2017 Jan 12;7:40799. doi: 10.1038/srep40799.
The morbidity rate of hypertriglyceridemic acute pancreatitis (HTG-AP) increased rapidly over the last decade. However an appropriate animal model was lacking to recapitulate this complicated human disease. We established a novel mice model of HTG-AP by poloxamer 407 (P-407) combined with caerulein (Cae). In our study, serum triglyceride levels of P-407 induced mice were elevated in a dose-dependent manner, and the pancreatic and pulmonary injuries were much severer in HTG mice than normal mice when injected with conventional dose Cae (50 ug/kg), what's more, the severity of AP was positively correlative with duration and extent of HTG. In addition, we found that a low dose Cae (5 ug/kg) could induce pancreatic injury in HTG mice while there was no obvious pathological injury in normal mice. Finally, we observed that HTG leaded to the increased infiltrations of macrophages and neutrophils in mice pancreatic tissues. In conclusion, we have developed a novel animal model of HTG-AP that can mimic physiological, histological, clinical features of human HTG-AP and it could promote the development of therapeutic strategies and advance the mechanism research on HTG-AP.
高脂血症性急性胰腺炎(HTG-AP)的发病率在过去十年中迅速上升。然而,缺乏合适的动物模型来重现这种复杂的人类疾病。我们通过聚氧乙烯醚 407(P-407)联合促胰液素(Cae)建立了一种新的 HTG-AP 小鼠模型。在我们的研究中,P-407 诱导的小鼠血清甘油三酯水平呈剂量依赖性升高,当用常规剂量 Cae(50μg/kg)注射时,HTG 小鼠的胰腺和肺损伤比正常小鼠严重得多,此外,AP 的严重程度与 HTG 的持续时间和程度呈正相关。此外,我们发现低剂量 Cae(5μg/kg)可诱导 HTG 小鼠发生胰腺损伤,而正常小鼠无明显病理损伤。最后,我们观察到 HTG 导致小鼠胰腺组织中巨噬细胞和中性粒细胞浸润增加。总之,我们已经建立了一种新的 HTG-AP 动物模型,能够模拟人类 HTG-AP 的生理、组织学和临床特征,它可以促进治疗策略的发展,并推进 HTG-AP 的机制研究。