Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University Graduate School of Veterinary Science, Osaka, Japan.
Laboratory of Veterinary Pathology, Osaka Metropolitan University Graduate School of Veterinary Science, Osaka, Japan.
J Vet Med Sci. 2023 Jun 13;85(6):657-666. doi: 10.1292/jvms.22-0569. Epub 2023 May 23.
Na/Ca exchangers (NCX) are an exchange transporter of Na and Ca ions on the plasma membrane. There are three types of NCX: NCX1, NCX2, and NCX3. We have been working for many years to understand the role of NCX1 and NCX2 in gastrointestinal motility. In this study, we focused on the pancreas, an organ closely related to the gastrointestinal tract, and used a mouse model of acute pancreatitis to investigate a possible role for NCX1 in the pathogenesis of pancreatitis. We characterized a model of acute pancreatitis induced by excessive doses of L-arginine. We administered the NCX1 inhibitor SEA0400 (1 mg/kg) 1 hr prior to L-arginine-induced pancreatitis and evaluated pathological changes. Mice treated with NCX1 inhibitors show exacerbation of the disease with decreased survival and increased amylase activity in response to L-arginine-induced experimental acute pancreatitis, and this exacerbation correlates with increased autophagy mediated by LC3B and p62. These results suggest that NCX1 has a role in regulating pancreatic inflammation and acinar cell homeostasis.
钠/钙交换器（NCX）是一种位于质膜上的 Na 和 Ca 离子交换转运体。NCX 有三种类型：NCX1、NCX2 和 NCX3。多年来，我们一直在努力研究 NCX1 和 NCX2 在胃肠道动力中的作用。在这项研究中，我们专注于胰腺这一与胃肠道密切相关的器官，并使用急性胰腺炎小鼠模型来研究 NCX1 在胰腺炎发病机制中的可能作用。我们对过量 L-精氨酸诱导的急性胰腺炎模型进行了特征描述。我们在 L-精氨酸诱导的胰腺炎发生前 1 小时给予 NCX1 抑制剂 SEA0400（1mg/kg），并评估了病理变化。用 NCX1 抑制剂处理的小鼠表现出疾病加重，其对 L-精氨酸诱导的实验性急性胰腺炎的反应中，存活率降低，淀粉酶活性增加，这种加重与 LC3B 和 p62 介导的自噬增加相关。这些结果表明，NCX1 在调节胰腺炎症和腺泡细胞内稳态方面发挥作用。
