Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

World J Gastroenterol. 2008 May 28;14(20):3249-53. doi: 10.3748/wjg.14.3249.

Abstract

Aim: To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats.

Methods: Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliary-pancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured. The TNF-alpha level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay (ELISA) kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed.

Results: MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-alpha level, pancreatic and pulmonary MPO activity (P < 0.05). Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity (P < 0.05).

Conclusion: The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Leupeptins / pharmacology*
  • Lung / drug effects*
  • Lung / enzymology
  • Lung / pathology
  • Lung Diseases / enzymology
  • Lung Diseases / etiology
  • Lung Diseases / prevention & control*
  • Male
  • Organ Size
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / complications
  • Pancreatitis / enzymology
  • Pancreatitis / prevention & control*
  • Peroxidase / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Taurocholic Acid
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cysteine Proteinase Inhibitors
  • Leupeptins
  • Proteasome Inhibitors
  • Tumor Necrosis Factor-alpha
  • Taurocholic Acid
  • Peroxidase
  • Amylases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde