[Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats].
OBJECTIVE
To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism.


METHODS
Thirty SD rats were randomly divided into 3 groups, namely the normoxic group, hyperoxic group, and hyperoxic with MG-132 treatment group, and rat models of hyperoxic exposure-induced lung injury were established in the latter two groups. After pathological grading of the lung injury under optical microscope and determination of the wet/dry weight ratio of the lung tissue, the expressions of ubiquitin protein and nuclear factor-kappaB (NF-kappaB) p56 and the activity of proteasome 20S and myeloperoxidase (MPO) were detected. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions in the lung tissue were also detected.


RESULTS
The rats with hyperoxic exposure showed obvious pulmonary edema and increased wet/dry weight ratio of the lung tissue (P<0.01), which were significantly alleviated with MG-132 treatment (P<0.01). Compared with the normoxic group, hyperoxic exposure resulted in significant lung pathologies (P<0.01), which was reduced after MG-132 treatment. Immunohistochemistry and Western blotting demonstrated increased expression of ubiquitin protein in the lung tissue after hyperoxic exposure (P<0.01), which was lowered by MG-132 treatment (P<0.01). Proteasome 20S activity was obviously enhanced in the hyperoxic group (P<0.01) but lowered by MG-132 treatment (P<0.01). Hyperoxic exposure also caused obviously enhanced MPO activity and expressions of NF-kappaB, TNF-alpha, and IL-6 (P<0.01), which were all reduced by MG-132 treatment (P<0.05).


CONCLUSIONS
MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways.
Huang
Yu-ge
YG
Graduate College of Southern Medical Unversity, Guangzhou 510515, China. kenbobozj@yahoo.com.cn
Feng
Zhi-chun
ZC
Yu
Yan-liang
YL
Xiao
Fang-fang
FF
D000818:Animals; D000831:Animals, Newborn; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005260:Female; D018496:Hyperoxia / Q000150:complications*; D015850:Interleukin-6 / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology*; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D015850:Interleukin-6; D007976:Leupeptins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D009195:Peroxidase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde