Y Lu1,2, J Wu1,2, W Jiang1,2, J Liu1,2, H Qie1,2, H Sun1,2, L Tang1,2. 1. School of Clinical Medicine, Southwest Jiaotong University, Chengdu 610063, China. 2. Center of General Surgery//Sichuan Provincial Key Laboratory of Pancreatic Injury and Repair, General Hospital of Western Theater Command, Chengdu 610083, China.
Abstract
OBJECTIVE: To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism. METHODS: Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting. RESULTS: Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP. CONCLUSION: APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP.
OBJECTIVE: To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism. METHODS: Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting. RESULTS: Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP. CONCLUSION: APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP.
Entities:
Keywords:
abdominal puncture drainage; autophagy; heme oxygenase-1; severe acute pancreatitis
Authors: Tiantian Wang; Chunyuan Chen; Lei Yang; Zhihui Zeng; Maojun Zeng; Wen Jiang; Lin Liu; Mingyi Zhao Journal: Zhong Nan Da Xue Xue Bao Yi Xue Ban Date: 2019-01-28
Authors: J Schmidt; D W Rattner; K Lewandrowski; C C Compton; U Mandavilli; W T Knoefel; A L Warshaw Journal: Ann Surg Date: 1992-01 Impact factor: 12.969