Acute pancreatitis (AP) is associated with impaired acinar cell autophagic flux, intracellular zymogen activation, cell necrosis and inflammation. Activation of the cholinergic system of vagus nerve has been shown to attenuate AP, but the effect of organ-intrinsic cholinergic system on pancreatitis remains unknown. In this study, we aim to examine the effect of α7 nicotinic acetylcholine receptor (α7nAChR) stimulation within the pancreas during AP. In vivo, AP was induced by caerulein plus LPS or ethanol plus palmitoleic acid in mice. In vitro, pancreatic acini were isolated and subjected to cholecystokinin (CCK) stimulation. Mice or acini were pre-treated with PNU-282987 (selective α7nAChR agonist) or methyllycaconitine citrate salt (selective α7nAChR antagonist). Pancreatitis severity, acinar cell injury, autophagic flux, and transcription factor EB (TFEB) pathway were analyzed. Both caerulein plus LPS in vivo and CCK in vitro led to an up-regulation of α7nAChR, indicating activation of pancreas-intrinsic α7nAChR signaling during AP. PNU-282987 decreased acinar cell injury, trypsinogen activation and pancreatitis severity. Conversely, methyllycaconitine citrate salt increased acinar cell injury and aggravated AP. Moreover, activation of α7nAChR by PNU-282987 promoted autophagic flux as indicated by reduced p62, increased LysoTracker staining and decreased number of autolysosomes with undegraded contents. Furthermore, PNU-282987 treatment significantly increased TFEB activity in pancreatic acinar cells. α7nAChR activation also attenuated pancreatic inflammation and NF-κB activation. Our results showed that activation of α7nAChR protected against experimental pancreatitis through enhancing TFEB-mediated acinar cell autophagy, suggesting that activation of pancreas-intrinsic α7nAChR may serve as an endogenous protective mechanism during AP.

急性胰腺炎（AP）与腺泡细胞自噬通量受损，细胞内酶原激活，细胞坏死和炎症有关。迷走神经胆碱能系统的激活已显示可减弱AP，但器官内源胆碱能系统对胰腺炎的作用仍未知。在这项研究中，我们旨在检查AP期间胰腺内α7烟碱乙酰胆碱受体（α7nAChR）刺激的作用。在体内，AP是由菜青素加脂多糖或乙醇加棕榈油酸诱导的。体外分离出胰腺腺泡并进行胆囊收缩素（CCK）刺激。小鼠或痤疮用PNU-282987（选择性α7nAChR激动剂）或柠檬酸甲基卡卡尼汀盐（选择性α7nAChR拮抗剂）进行预处理。胰腺炎严重程度，腺泡细胞损伤，自噬通量和转录因子EB（TFEB）途径进行了分析。体内青霉素加脂多糖和体外CCK导致α7nAChR的上调，表明在AP期间胰腺内源性α7nAChR信号的激活。PNU-282987减少了腺泡细胞损伤，胰蛋白酶原激活和胰腺炎的严重程度。相反，柠檬酸甲基卡卡尼汀盐增加了腺泡细胞损伤并加重了AP。此外，PNU-282987对α7nAChR的激活促进了自噬通量，如p62减少，LysoTracker染色增加和内容物未降解的自溶酶体数量减少。此外，PNU-282987治疗显着提高了胰腺腺泡细胞中的TFEB活性。α7nAChR激活还减弱了胰腺炎症和NF-κB激活。我们的结果表明，α7nAChR的激活可通过增强TFEB介导的腺泡细胞自噬来保护免受实验性胰腺炎的侵害，