Development of a novel model of hypertriglyceridemic acute pancreatitis in mice.

Development of a novel model of hypertriglyceridemic acute pancreatitis in mice.
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高甘油三酯血症小鼠急性胰腺炎新模型的建立

DOI:
10.1038/srep40799
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发表时间:
2017-01-12
期刊:
影响因子:
4.6
通讯作者:
Li J
Li J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pan Y;Li Y;Gao L;Tong Z;Ye B;Liu S;Li B;Chen Y;Yang Q;Meng L;Wang Y;Liu G;Lu G;Li W;Li J

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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概括这种复杂的人类疾病。我们采用泊洛沙姆407(P-407)联合雨蛙素(Cae)建立了一种新的HTG-AP小鼠模型。本研究发现,P-407诱导的小鼠血清甘油三酯水平呈剂量依赖性升高,注射常规剂量Cae(50 μ g/kg)后,HTG小鼠胰腺和肺损伤较正常小鼠严重,且AP的严重程度与HTG的持续时间和程度呈正相关。另外,我们发现低剂量的Cae(5 μ g/kg)可引起HTG小鼠胰腺损伤,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,我们建立了一种能够模拟人HTG-AP生理、组织学、临床特征的新型HTG-AP动物模型,为HTG-AP的治疗策略和机制研究提供了新的思路。
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.