title: Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats.
abstract: OBJECTIVE
  To determine the optimal dosage and mechanism of Ginkgolide B (BN52021) on severe acute pancreatitis (SAP) of rats.
  
  
  METHODS
  Seventy male Wistar rats were randomly divided into seven groups (10 for each group). Sham-operation group (SO), SAP model group (SAP), dimethyl sulfoxide (DMSO) contrast group (DMSO), and groups treated with 2.5 mg/kg BN52021 (BN1), 5 mg/kg BN52021 (BN2), 10 mg/kg BN52021 (BN3), and 20 μg/kg Sandostatin (SS). The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct. The rats of SO, DMSO and BN52021 were injected with 0.9% NaCl, 0.5% DMSO and BN52021 through femoral vein 15 min after the operation. The SS group was injected with Sandostatin subcutaneously. All rats were anaesthetized at 6 h after operation, and venous blood was collected to determine the levels of serum amylase and phospholipase A2 (PLA₂), and pancreas tissue was harvested and stained.
  
  
  RESULTS
  There was no significant difference between the SAP and DMSO groups in serum amylase level, PLA₂, ascites and pathologic score, but significant difference was found in SAP/DMSO groups compared with those in SO group (P < 0.05) and the levels of serum amylase, PLA₂, ascites, and pathologic score were lower in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). However, among BN1, BN2, BN3 and SS groups, BN2 had the best effect in decreasing the levels of serum amylase and PLA₂ (P < 0.05). Expression of platelet activating factor (PAF) receptor (PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups, or among BN1, BN2, BN3 and SS groups, but there was remarkable difference between SAP/DMSO group and SO group (P < 0.05), and expression of PAFR mRNA and protein was higher in the BN1, BN2, BN3 and SS groups than in the SAP and DMSO groups (P < 0.05). PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry.
  
  
  CONCLUSIONS
  By iv injection, 5 mg/kg of BN52021 is the optimal dosage for SAP rats. BN52021 may inhibit the interaction/binding of PAF with PAFR.
authors.affiliation: Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital of Medical College of Chinese People's Armed Police Force, Tianjin 300162, China.
authors.forename: Run-Li
authors.initials: RL
authors.lastname: Ji
authors.forename: Shi-Hai
authors.initials: SH
authors.lastname: Xia
authors.forename: Yao
authors.initials: Y
authors.lastname: Di
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism; D054467:Phospholipases A2 / Q000097:blood; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B; D054467:Phospholipases A2; D000681:Amylases