Proteasome inhibition attenuates lung injury induced by intestinal ischemia reperfusion in rats.
The aim of this study is to investigate the role of proteasome in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R) by examining the effect of the proteasome inhibitor lactacystin on neutrophil infiltration, intracellular adhesion molecule-1 (ICAM-1) expression and nuclear factor kappa B (NF-kappaB) activation. Thirty-two Wistar rats were divided into (1) control, (2) intestinal I/R, (3) 0.2 mg/kg lactacystin pretreated, and (4) 0.6 mg/kg lactacystin pretreated groups (n=8). Injuries in lung and intestine were induced by intestinal I/R, and were characterized by histological edema, hemorrhage and infiltration of inflammatory cells. The results showed a significant increase in serum creatine kinase B (CK-B) and lung water content in intestine and lung injuries. As compared with the control group, the myeloperoxidase (MPO) activity in intestine and lung as well as the serum TNF-alpha level increased significantly in intestinal I/R group. Simultaneously, expression of ICAM-1 and NF-kappaB p65 was also observed in the I/R group. Pre-treatment with lactacystin markedly reduced 20S proteasome activity in circulating white blood cells and ameliorated intestine and lung injuries. These results demonstrated that the proteasome participates in the pathogenesis of lung injury induced by intestinal I/R. Lactacystin as a proteasome inhibitor can prevent this kind of injury by decreasing ICAM-1 and TNF-alpha production via the inhibition of NF-kappaB activation.
Tian
Xiao-Feng
XF
Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China. txfdl@hotmail.com
Zhang
Xue-Song
XS
Li
Ying-Hua
YH
Wang
Zheng-Zheng
ZZ
Zhang
Feng
F
Wang
Li-Ming
LM
Yao
Ji-Hong
JH
D000818:Animals; D001834:Body Water / Q000378:metabolism; D052276:Creatine Kinase, BB Form / Q000097:blood; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000097:blood; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D061988:Proteasome Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D052276:Creatine Kinase, BB Form; D046988:Proteasome Endopeptidase Complex