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Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis
Author(s) -
Liu Ruixia,
Qi Haiyu,
Wang Jing,
Wang Yan,
Cui Lijian,
Wen Yan,
Yin Chenghong
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12584
Subject(s) - ulinastatin , medicine , pathophysiology , pancreatitis , acute pancreatitis , renin–angiotensin system , pancreas , endocrinology , angiotensin ii , angiotensin receptor , angiotensin converting enzyme , receptor , ace inhibitor , pancreatic disease , receptor expression , pharmacology , blood pressure
Background and Aim Ulinastatin is a drug used effectively to alleviate symptoms and improve the pathophysiology of various types of pancreatitis. However, the molecular mechanism responsible for its action remains unknown. Therefore, we further explore the therapeutic effects of ulinastatin and investigate possible molecular pathways modulated by this drug in the development of severe acute pancreatitis ( SAP ). Methods SAP mouse model was created by administering intraperitoneal injections of cerulein and lipopolysaccharide. Pancreatic injury was assessed by performing biochemical and histological assays and by measuring the inflammatory response of the pancreas. Specifically, we examined changes in the expression of components of the rennin–angiotensin system ( RAS ), including angiotensin‐converting enzyme ( ACE )‐angiotensin II ( Ang II )‐angiotensin type 1 receptor ( AT ‐1 R ), and ACE 2‐Ang‐(1–7)–Mas receptor. Results When SAP mouse models were treated with ulinastatin at a dosage of 50 000 U /kg body weight, we found, through biochemical and histopathological analyses, that the pancreatic injury was significantly ameliorated. Administration of ulinastatin to SAP mice led to increased expression of ACE 2, Ang‐(1–7), and Mas receptor, decreased expression of serum A ng II and pancreatic AT ‐1 R , and no alterations in the expression of pancreatic ACE and A ng II when compared to cerulein‐treated control group that did not receive ulinastatin. Conclusions This study shows that ulinastatin has differential effects on the two axes of the RAS during SAP . Our results further suggest that upregulation of components of the ACE 2‐Ang‐(1–7)–Mas pathway might be an important mechanism contributing to the therapeutic role of ulinastatin in alleviating pancreatitis‐associated symptoms.