The Experimental Study Of Protective Effect On Tauroursodeoxycholic Acid In Cerulein Induced Acute Pancreatitis

Objective The study was aimed toward investigating the effects of TUDCA in an acute experimental pancreatitis model in vivo in order to provide new treatment options for clinical therapy of acute pancreatitis.Methods The 96 experimental SD rats were randomly divided into four groups, Na Cl group, TUDCA control group, CER group, TUDCA treatment groups. The rats in the model were given the preparation of pre-AP administration(or placebo), before using bombesin-induced animal model of AP.Acute pancreatitis was induced in SD rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein(Bi P), phosph-orylated protein kinase-like ER kinase(p PERK), X-box binding protein(XBP)-1, phosphorylated c-Jun NH2-terminal kinase(p JNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue.Results 1.TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung.2.Furthermore, TUDCA prevented caerulein-induced Bi P upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of p JNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including p PERK signaling and activation of downstream targets.Conclusions ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA.The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA alleviate ER stress response of acute pancreatitis in general through raising Bi P and lowering XBP-1 splicing, inhibiting activation of caspase12 and caspase3, accelerating down p JNK and other ways.TUDCA has a cytoprotective potential in the exocrine pancreas.