Tauroursodeoxycholic acid attenuates severe acute pancreatitis-induced liver injury in rat models

Abstract

Objective To investigate the effect and mechanism of tauroursodeoxycholic acid (TUDCA) on severe acute pancreatitis (SAP)-induced liver injury in rat model. Methods Thirty SD rats were randomly divided into three groups(10 in each ):shame operation group(SO group),severe acute pancreatitis group(SAP group) and tauroursodeoxycholic acid group(TUDCA group).The SAP model was established by retrogradely injecting 5% sodium taurocholate (STC) solution (1 mL/kg) into pancreaticobiliary duct. The TUDCA group rats were intraperi- toneally injected with TUDCA(400 mg/kg·d-1) for three days continuously fore establishing models and the SAP and SO group rats were intraperitoneally injected with the same volume of saline. Rats were sacrificed 12 hrs after modeling, and then peripheral blood and part of pancreatic and liver tissues were collected. The level of amylase(AMY), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) was detected by automatic biochemical analyzer. The expression of interleukin-6(IL-6) was detected by enzyme-linked immunosorbent assay (ELISA).The histo-pathological profile of pancreas and liver was examined by hematoxylin-eosin (HE) staining microscopy and liver apoptosis was observed by in situ terminal deoxynucleotide transferase labeling (TUNEL). The expression level of glucose-regulating protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), nuclear factor-κB p65(NF-κB p65) and caspase-3 protein was determined by Western blot. Results Compared with SO group, the expression level of AMY,AST, ALT and IL-6 was increased in SAP group(P＜0.05); pancreas and liver necrosis and hepatocyte apoptosis were found to be more significant and the level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein increased (P＜0.05). Compared with SAP group, the expression of AMY, AST, ALT and IL-6 was reduced in TUDCA group and pancreas and liver necrosis and hepatocyte apoptosis were less severe. The level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein significantly decreased(P＜0.05). Conclusions TUDCA may have a protective mechanism to alleviate pancreatitis-induced severe and acute liver injury in rats by reducing the occurrence of endoplasmic reticulum stree(ERS), alleviating the inflammation and apoptosis as well as inhibiting PERK signaling pathway.

Keywords

• tauroursodeoxycholic acid|endoplasmic reticulum stress|severe acute pancreatitis