Alteration of C/EBPs and endoplasmic reticulum stress related molecules expression in pancreatic tissues in rats with hypertriglyceridemia related acute pancreatitis / 中华胰腺病杂志

ABSTRACT

Objective To investigate the alteration of C/EBP α,C/EBP β and endoplasmic reticulum stress (ERS) related molecules (IRE1α and sXBP1) expression in pancreatic tissues in rats with hypertriglyceridemia related acute pancreatitis.Methods Ninety six Sprague Dawley (SD) rats were divided into 4 groupscontrol group,hypertriglyceridemia (HTG) group (n =24,fed with high fat diet for 2 weeks),AP group (n =24),HTG + AP group (n =24),and AP was induced by peritoneal injection of cerulein.The rats were sacrificed at 3,6,9,24 h after AP induction,respectively.The pathological changes of the pancreatic tissues were observed and scored by HE staining.Plasma levels of IL-1β,IL-6 and TNF-α were measured by ELISA.The expression of IRE1α,sXBP1,C/EBPoα,C/EBPβ mRNA were analyzed by real time PCR.The expressions of IRE1α,sXBP1,NF-kB,C/EBPα and C/EBPβ protein were determined by Western Blot.The expressions of C/EBPα and C/EBPβ proteins were also determined by immunohitochemistry.Results After two weeks of high fat diet,serum levels of triglyceride(TG) and total cholesterol (TC) in HTG group,HTG + AP group were much higher than those of the control group,and the difference was statistically significant (P ＜ 0.05).The pancreatic tissue injury was more severe in HTG + AP group,particularly at 9 h (P ＜ 0.05).And plasma IL-1β,IL-6 and TNF-α levels were also much higher in HTG + AP group when compared with that of AP group,the differences were all significant at 9 h (P=0.011;P=0.034;P =0.027).After AP induction,IRE1,sXBP1,C/EBP and C/EBPβ mRNA began to be up-regulated at 3 h,and IRE1 mRNA reached the highest level at 24 h,sXBP1 mRNA at 9 h,while C/EBP and C/EBPβ mRNA reached the highest level at 6 h.Compared with AP group,IRE1,sXBP1,C/EBP and C/EBPβ mRNA levels were much higher in HTG + AP group.In addition,as to IRE1 and sXBP1 mRNA,the difference was significant at 3,6,9,24 h,and C/EBP mRNA at 6,9,24 h,C/EBPβ mRNA at 6 and 9 h (P ＜ 0.05).After AP induction,IRE1α,sXBP1 and NF-kB proteins in the pancreatic tissue began to be up-regulated at 3 h,and all reached the highest level at 9 h.IRE1α,sXBP1 and NF-kB proteins were up-regulated more obviously in HTG + AP group,and the up-regulation in HTG + AP group was higher than that in AP group,and the high expressions of C/EBPα and C/EBPβ proteins could only be detected at 6 and 9 h in the HTG + AP group,while there was no expression detected in AP group.Conclusions C/EBPα,C/EBPβ,IRE1α and sXBP1 may be involved in the pathogenesis of HTG related AP,and IRE1α/sXBP1 pathway and C/EBPoα,C/EBPβ may mediate the pathologic injury and inflammation process of HTG related AP.