Phillygenin rescues impaired autophagy flux by modulating the PI3K/Akt/mToR signaling pathway in a rat model of severe acute pancreatitis.

To investigate the mechanism of pancreatic alveolar cell autophagy in rats with severe acute pancreatitis (SAP) by phillygenin (PHI) based on the PI3K/Akt/mToR pathway. Rats were randomly divided into control group (CON group), SAP model group (SAP group) and PHI treatment group (SAP+PHI group), with 10 rats in each group. 5% sodium taurocholate was injected retrogradely into the biliopancreatic duct to establish a SAP rat model, and PHI was injected intraperitoneally into the pancreas after successful establishment of the model. The colorimetric assay was used to determine serum amylase and lipase activity levels. Pancreatic morphology and histological changes were assessed by H&E staining. Autophagy-related indices were determined by immunohistochemistry: LC3-II, P62, LAMP. Autophagy pathway-related indices were determined by western blotting assay: p-PI3K, PI3K, p-Akt, Akt, p-mToR, mToR. Autophagy vesicle alteration. Compared with the SAP group, the SAP+PHI group showed a decrease in amylase, lipase and pathological score, an increase in the expression of LAMP-2, and a decrease in the expression of p62, p-PI3K, p-Akt and p-mToR, with a statistically significant difference (p < 0.05). Electron microscopy showed that autophagic flux was restored and accumulated autophagic vehicles were relatively reduced by PHI intervention. PHI can rescue the impaired autophagic flux by inhibiting the PI3K/Akt/mToR pathway, allowing abnormal autophagic vesicles to complete autophagy to protect the rat.