Gene expression profiling and endothelin in acute experimental pancreatitis  

作　　者：Helieh S Oz Ying Lu Louis P Vera-Portocarrero Pei Ge Ada Silos-Santiago Karin N Westlund 

机构地区：[1]Department of Physiology, College of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, United States [2]Department of Internal Medicine, College of Medicine, University of Kentucky Medical Center, Lexington, KY 40536, United States [3]Department of Anatomy and Neuroscience, University of Texas Medical Branch, Galveston, TX 77555, United States [4]Medtronics Inc., Minneapolis, MN 55432, United States [5]Ironwood Pharmaceuticals, Cambridge, Ironwood Pharmaceuticals, Cambridge, MA 02141, United States

出　　处：《World Journal of Gastroenterology》2012年第32期4257-4269,共13页世界胃肠病学杂志（英文版）

基　　金：Supported by National Institutes of Health Grants,No. NS039041,to Westlund KN and DE19177,to Oz HS

摘　　要：AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS:Dibutyltin dichloride(DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia(DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin(ET) receptor antagonists [ET-A(BQ123) and ET-B BQ788)].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies(edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors(cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory;extracellular matrix;structural;channel/receptor/transporter;signaling transduction;transcription/translation-related;antioxidants/chaperones/heat shock;pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in animals with pancreatic inflammation and visceral pain-related beAIM：To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS：Dibutyltin dichloride（DBTC） is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia（DRG） were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin（ET） receptor antagonists [ET-A（BQ123） and ET-B BQ788）].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS：Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies（edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells） and the painrelated behaviors（cutaneous secondary mechanical and thermal hypersensitivity）.Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families：circulatory/acute phase/immunomodulatory;extracellular matrix;structural;channel/receptor/transporter;signaling transduction;transcription/translation-related;antioxidants/chaperones/heat shock;pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in animals with pancreatic inflamm

关 键 词：Gene expression Endothelin receptors Pancreatitis Pain Dibutyltin dichloride Hypersensitivity Hyperalgesia 

分 类 号：R576[医药卫生—消化系统]