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首页> 外文期刊>American Journal of Physiology >Ketamine and xylazine effects in murine model of acute pancreatitis
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Ketamine and xylazine effects in murine model of acute pancreatitis

机译：急性胰腺炎鼠模型的氯胺酮和木嗪作用

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摘要

Ketamine and xylazine (Ket/Xyl) are anesthetic agents that target neural pathways and are commonly used in combination in mouse studies. Since neural pathways can modulate acute pancreatitis severity, we asked if Ket/Xyl affect disease severity. C57BL/6 mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis. Mice were also treated with and without ketamine, xylazine, and Ket/Xyl before pancreatitis induction in vivo and in vitro. Ket/Xyl pretreatment in vivo increased selected parameters of pancreatitis severity such as trypsin activity and edema; these effects were predominantly mediated by xylazine. Ket/Xyl also changed markers of autophagy. These in vivo effects of Ket/Xyl were not attenuated by atro-pine. The drugs had no little to no effect on pancreatitis responses in isolated pancreatic cells or lobules. These findings suggest that Ket/Xyl administration can have substantial effect on acute pancreatitis outcomes through nonmuscarinic neural pathways. Given widespread use of this anesthetic combination in experimental animal models, future studies of inflammation and injury using Ket/Xyl should be interpreted with caution. NEW & NOTEWORTHY Ketamine and xylazine anesthetic agent administration before acute pancreatitis induction in mice lead to changes in pancreatitis responses independent of acute pancreatitis induction. Future studies should consider the potential effects of anesthesia administration when studying disease processes associated with inflammation and injury.
机译：氯胺酮和甲苯噻嗪（Ket/Xyl）是针对神经通路的麻醉剂，通常在小鼠研究中联合使用。由于神经通路可以调节急性胰腺炎的严重程度，我们询问Ket/Xyl是否会影响疾病的严重程度。C57BL/6小鼠每六小时注射一次雨蛙素，以诱导轻度急性胰腺炎。在体内和体外诱导胰腺炎之前，小鼠也接受氯胺酮、甲苯噻嗪和Ket/Xyl的治疗。体内Ket/Xyl预处理增加了胰腺炎严重程度的某些参数，如胰蛋白酶活性和水肿；这些作用主要由二甲苯嗪介导。Ket/Xyl也改变了自噬标记物。Ket/Xyl的这些体内效应未被阿托品减弱。这些药物对分离的胰腺细胞或小叶的胰腺炎反应没有影响。这些发现表明，Ket/Xyl给药可通过非甲肾上腺素神经通路对急性胰腺炎的预后产生实质性影响。鉴于这种麻醉剂组合在实验动物模型中的广泛使用，未来使用Ket/Xyl进行的炎症和损伤研究应谨慎解释。在小鼠急性胰腺炎诱导前服用新的值得注意的氯胺酮和甲苯噻嗪麻醉剂会导致胰腺炎反应的变化，而非急性胰腺炎诱导。未来的研究应该考虑麻醉管理在研究与炎症和损伤相关的疾病过程中的潜在影响。

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