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


CONCLUSIONS
The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.
Department of General Surgery, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. 2002chenxi@163.com
Xi
X
Chen
Shun-Le
SL
Li
Tao
T
Wu
Ji-Dong
JD
Liu
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007976:Leupeptins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D009195:Peroxidase; D000681:Amylases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde