College Pharmacy and Biological Engineering, Chongqing University of Technology, Chongqing, 400054, China.
Department of Pharmacy, Guizhou Provincial People's Hospital, 550002, Guiyang, China.
Biochem Biophys Res Commun. 2022 Dec 20;635:236-243. doi: 10.1016/j.bbrc.2022.10.044. Epub 2022 Oct 14.
Acute pancreatitis (AP) is a common inflammatory disease of the digestive system. Mitochondrial calcium uniporter (MCU) mediates mitochondrial uptake of Ca and plays an important role in calcium homeostasis. However, it is undefined whether AP can be relieved by inhibiting MCU. This study aimed to study the therapeutic potential of Ruthenium red (RuR), a MCU inhibitor, in AP mice model and primary acinar cells. Cell injury and AP mice model was induced by caerulein. RuR alleviated CER-AP evidenced by reduced serum lipase, TNF-α, and pancreatic MPO levels, less severe pancreatic pathology damage, and decreased inflammatory cell infiltration. In freshly isolated pancreatic acinar cells, RuR diminished cell necrosis with effect on suppressing the expression of MCU. RuR also decreased levels of cytosolic calcium and ROS, preventing mitochondrial membrane potential loss, ATP depletion and MPTP opening. The present findings indicate that inhibit MCU by RuR has a beneficial effect in AP by preventing calcium overload, mitochondrial dysfunction, and cell necrosis.
急性胰腺炎（AP）是一种常见的消化系统炎症性疾病。线粒体钙单向转运蛋白（MCU）介导线粒体摄取 Ca2+，在钙稳态中发挥重要作用。然而，抑制 MCU 是否可以缓解 AP 尚未明确。本研究旨在探讨 MCU 抑制剂钌红（RuR）在 AP 小鼠模型和原代胰腺腺泡细胞中的治疗潜力。采用促蓝蛋白诱导细胞损伤和 AP 小鼠模型。RuR 减轻 CER-AP，表现为血清脂肪酶、TNF-α 和胰腺髓过氧化物酶水平降低，胰腺病理损伤减轻，炎症细胞浸润减少。在新鲜分离的胰腺腺泡细胞中，RuR 抑制 MCU 的表达，减少细胞坏死。RuR 还降低细胞浆钙和 ROS 水平，防止线粒体膜电位丧失、ATP 耗竭和 MPTP 开放。这些发现表明，RuR 通过抑制 MCU 可通过防止钙超载、线粒体功能障碍和细胞坏死对 AP 产生有益影响。
