Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats / 南方医科大学学报
Journal of Southern Medical University
; (12): 970-978, 2009.
Article
in Zh
| WPRIM
| ID: wpr-268796
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pathology
/
Pharmacology
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Random Allocation
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Cysteine Proteinase Inhibitors
/
NF-kappa B
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Interleukin-6
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Tumor Necrosis Factor-alpha
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Rats, Sprague-Dawley
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Peroxidase
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Hyperoxia
Type of study:
Prognostic_studies
Limits:
Animals
Language:
Zh
Journal:
Journal of Southern Medical University
Year:
2009
Type:
Article