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.
Chen
Xi
X
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
Li
Shun-Le
SL
Wu
Tao
T
Liu
Ji-Dong
JD
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