Development of a new mouse model of acute pancreatitis induced by administration of L-arginine
Development of a new mouse model of acute pancreatitis induced by administration of L-arginine
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DOI：
10.1152/ajpgi.00167.2006
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发表时间：
2007-04-01
影响因子：
4.5
通讯作者：
Saluja, Ashok K.
中科院分区：
文献类型：
--
作者：
Dawra, Rajinder;Sharif, Rifat;Saluja, Ashok K.
急性胰腺炎的发病机制尚不完全清楚。模拟人类疾病的实验动物模型对于更好地了解疾病的病理生理学和评估潜在的治疗药物至关重要。鉴于小鼠基因组是完全已知的，并且有大量具有各种遗传缺失的菌株，因此有多种可靠的急性胰腺炎小鼠模型是有利的。目前，只有一种主要的小鼠急性胰腺炎模型，即给予高刺激剂量的胆囊收缩素或其类似物小蛋白。因此，本研究的目的是建立另一种小鼠急性胰腺炎模型。本实验以C57BL/ 6小鼠腹腔注射L-精氨酸，每次4 g/ kg，间隔1 h。在注射后不同时间点检测血清淀粉酶、髓过氧化物酶和组织病理学，以评估胰腺和肺的损伤。我们发现，注射L-精氨酸后，血浆淀粉酶和胰腺髓过氧化物酶显著升高，并伴有明显的组织病理学改变。胰腺损伤发展缓慢，并在72小时达到峰值。损伤峰值后，损伤区域含有胶原纤维，天狼星红染色增加。相反，d -精氨酸或其他氨基酸不会对胰腺造成损伤。此外，胰腺的急性炎症与肺损伤有关。我们的研究结果表明，给小鼠L-精氨酸会导致严重的急性胰腺炎。该模型有助于阐明胰腺炎的病理生理学。
The pathogenesis of acute pancreatitis is not fully understood. Experimental animal models that mimic human disease are essential to better understand the pathophysiology of the disease and to evaluate potential therapeutic agents. Given that the mouse genome is known completely and that a large number of strains with various genetic deletions are available, it is advantageous to have multiple reliable mouse models of acute pancreatitis. Presently, there is only one predominant model of acute pancreatitis in mice, in which hyperstimulatory doses of cholecystokinin or its analog caerulein are administered. Therefore, the aim of this study was to develop another mouse model of acute pancreatitis. In this study, C57BL/ 6 mice were injected intraperitoneally with L- arginine in two doses of 4 g/ kg each, 1 h apart. Serum amylase, myeloperoxidase, and histopathology were examined at varying time points after injection to assess injury to the pancreas and lung. We found that injection of L- arginine was followed by significant increases in plasma amylase and pancreatic myeloperoxidase accompanied by marked histopathological changes. The injury to the pancreas was slow to develop and peaked at 72 h. Subsequent to peak injury, the damaged areas contained collagen fibers as assessed by increased Sirius red staining. In contrast, D-arginine or other amino acids did not cause injury to the pancreas. In addition, acute inflammation in the pancreas was associated with lung injury. Our results indicate that administration of L- arginine to mice results in severe acute pancreatitis. This model should help in elucidating the pathophysiology of pancreatitis.