Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021

World J Gastroenterol. 2007 Jun 7;13(21):2992-8. doi: 10.3748/wjg.v13.i21.2992.

Abstract

Aim: To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B).

Methods: Wistar male rats were randomly assigned to the negative control group (NC group), SAP model group (SAP group), and BN52051-remedy group (BN group), and each of the groups was divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected.

Results: Serum amylase and pathological results showed the that SAP model was successfully prepared, BN52021 was able to decrease serum amylase, and the pathological ratings in BN group at 3 h, 6 h, and 12 h significantly decreased compared with those in the SAP group (8.85 +/- 0.39 vs 5.95 +/- 0.19, 9.15 +/- 0.55 vs 5.55 +/- 0.36, 10.10 +/- 0.65 vs 6.72 +/- 0.30, P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups, which increased gradually in early stage, reached a peak at 3 h (0.71 +/- 0.14 vs 0.54 +/- 0.14, 0.69 +/- 0.13 vs 0.59 +/- 0.04, P < 0.05), and decreased gradually later. There were significant differences at each time point except 1 h and 2 h, when compared with those in the NC group (0.71 +/- 0.14 or 0.69 +/- 0.13 vs 0.47 +/- 0.10, 0.38 +/- 0.08 or 0.59 +/- 0.04 vs 0.47 +/- 0.09, 0.25 +/- 0.07 or 0.29 +/- 0.05 vs 0.46 +/- 0.10, 0.20 +/- 0.06 or 0.20 +/- 0.04 vs 0.43 +/- 0.09, P < 0.05), whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h, when compared with those in the NC group (0.90 +/- 0.02 or 0.80 +/- 0.05 vs 0.48 +/- 0.02, 1.69 +/- 0.06 or 1.58 +/- 0.02 vs 0.48 +/- 0.03, 1.12 +/-0.10 or 0.98 +/- 0.03 vs 0.49 +/- 0.09, 1.04 +/- 0.14 or 0.87 +/- 0.02 vs 0.52 +/- 0.08, 0.97 +/- 0.16 or 0.90 +/- 0.05 vs 0.49 +/- 0.10, P < 0.05), whereas there was no significant difference between the BN group and the SAP group.

Conclusion: PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Gene Expression Regulation / drug effects*
  • Ginkgolides / pharmacology*
  • Ginkgolides / therapeutic use
  • Lactones / pharmacology*
  • Lactones / therapeutic use
  • Male
  • Pancreatitis / drug therapy
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology
  • Platelet Activating Factor / genetics
  • Platelet Activating Factor / metabolism
  • Platelet Membrane Glycoproteins / genetics
  • Platelet Membrane Glycoproteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Fibrinolytic Agents
  • Ginkgolides
  • Lactones
  • Platelet Activating Factor
  • Platelet Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • ginkgolide B
  • Amylases