Targeted Inhibition of Pancreatic Acinar Cell Calcineurin Is a Novel Strategy to Prevent Post-ERCP Pancreatitis

详细信息    查看全文

• 作者：Abrahim I. Orabi¹ ; ^&lowast ; ; Li Wen¹ ; ^&lowast ; ; Tanveer A. Javed¹ ; Tianming Le¹ ; Ping Guo² ; Subramaniam Sanker¹ ; David Ricks² ; Kristy Boggs¹ ; John F. Eisses¹ ; Carlos Castro³ ; Xiangwei Xiao² ; Krishna Prasadan² ; Farzad Esni² ; George K. Gittes² ; Sohail Z. Husain¹ ; ^{sohail.husain@chp.edu}
• 关键词：Adeno-Associated Virus ; Calcineurin B1 ; FK506 ; Cyclosporine A ; Intraductal Delivery
• 刊名：CMGH Cellular and Molecular Gastroenterology and Hepatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：3
• 期：1
• 页码：119-128
• 全文大小：3912 K
• 卷排序：3

文摘

There is a pressing need to develop effective preventative therapies for post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo.MethodsWe used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel adeno-associated virus–pancreatic elastase improved Cre (I–iCre) into the pancreatic duct of a calcineurin floxed line.ResultsWe found that PEP is dependent on acinar cell calcineurin in vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, largely can prevent PEP.ConclusionsThese results provide the impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP.