The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis
The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis
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DOI：
10.1089/ars.2011.4065
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发表时间：
2011-11-01
影响因子：
6.6
通讯作者：
Rakonczay, Zoltan, Jr.
中科院分区：
文献类型：
--
作者：
Biczo, Gyoergy;Hegyi, Peter;Rakonczay, Zoltan, Jr.
目的：腹腔注射大剂量碱性氨基酸、L-精氨酸或L-鸟氨酸，可诱发啮齿动物急性胰腺炎，但介导胰腺毒性的机制仍不清楚。另一种碱性氨基酸 L-赖氨酸也被证明会导致胰腺腺泡细胞损伤。该研究的目的是深入了解 L-赖氨酸损伤大鼠外分泌胰腺的机制，特别是表征 L-赖氨酸诱导的线粒体损伤的动力学，以及急性胰腺炎特征的病理反应（包括抗氧化系统的改变）。结果：我们发现腹腔注射 2 g/kg L-赖氨酸可诱发重症急性坏死性胰腺炎。 L-赖氨酸给药会在胰蛋白酶原和促炎转录因子核因子 kappa B (NF-kappa B) 激活之前引起早期胰腺线粒体损伤，通常认为这两种因子在急性胰腺炎的发展中发挥重要作用。我们的数据表明，L-赖氨酸会损害离体胰腺线粒体的三磷酸腺苷合酶活性，但不会损害肝脏线粒体。创新与结论：总而言之，大剂量L-赖氨酸引起的早期线粒体损伤可能导致急性胰腺炎的发生，而与胰腺胰蛋白酶原和NF-κB激活无关。抗氧化剂。氧化还原信号。 15、2669-2681。
Aims: Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results: We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-kappa B (NF-kappa B), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion: Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-kappa B activation. Antioxid. Redox Signal. 15, 2669-2681.