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Vascular endothelial growth factor induces inflammatory injury of pancreatic tissue by activating autophagy in hyperlipidemic acute pancreatitis rats 

WANG Ya-Ping^*, ZHAO Zhen, TANG Li, ZHU Zhi-Yong

Digestive Department of Wuxi Huishan District People’s Hospital, Wuxi 214187, China

Abstract

This study was to investigate the changes of autophagy in pancreatic tissue cells from hyperlipidemic acute pancreatitis (HLAP) rats and the molecular mechanism of autophagy to induce inflammatory injury in pancreatic tissue cells. Male Sprague Dawley (SD) rats were intraperitoneally injected with caerulein to establish acute pancreatitis (AP) model and then given a high fat diet to further prepare HLAP model. The HLAP rats were treated with autophagy inducer rapamycin or inhibitor 3-methyladenine. Pancreatic acinar (AR42J) cells were treated with caerulein to establish HLAP cell model. The HLAP cell model were treated with rapamycin or transfected with vascular endothelial growth factor (VEGF) siRNA. The inflammatory factors in serum and cell culture supernatant were detected by ELISA method. The histopathological changes of pancreatic tissue were observed by HE staining. The changes of ultrastructure and autophagy in pancreatic tissue were observed by electron microscopy. The expression levels of Beclin-1, microtubule- associated protein light chain 3-II (LC3-II), mammalian target of rapamycin complex 1 (mTORC1), and VEGF were measured by immunohistochemistry and Western blot. The results showed that, compared with control group, the autophagy levels and inflammatory injury of pancreatic tissue cells from HLAP model rats were obviously increased, and these changes were aggravated by rapamycin treatment, but alleviated by 3-methyladenine treatment. In HLAP cell model, rapamycin aggravated the autophagy levels and inflammatory injury, whereas VEGF siRNA transfection increased mTORC1 protein expression, thus alleviating the autophagy and inflammatory injury of HLAP cell model. These results suggest that VEGF-induced autophagy plays a key role in HLAP pancreatic tissue cell injury, and interference with VEGF-mTORC1 pathway can reduce the autophagy levels and alleviate the inflammatory injury. The present study provides a new target for prevention and treatment of HLAP.

Key words: hyperlipidemic acute pancreatitis; autophagy; vascular endothelial growth factor; mammalian target of rapamycin complex 1

Received: 　　Accepted:

Corresponding author: 王亚平　　E-mail: rose19820721@126.com

DOI: 10.13294/j.aps.2022.0011

Citing This Article：

WANG Ya-Ping, ZHAO Zhen, TANG Li, ZHU Zhi-Yong. Vascular endothelial growth factor induces inflammatory injury of pancreatic tissue by activating autophagy in hyperlipidemic acute pancreatitis rats . Acta Physiol Sin 2022; 74 (2): 225-236 (in Chinese with English abstract).