期刊
LIFE SCIENCES
卷 198, 期 -, 页码 112-118出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.02.039
关键词
Lipoxin A4 (LXA4); Obesity-related glomerulopathy (ORG); Inflammation; Nuclear factor-kappa B (NF-kappa B); Mitogen-activated protein kinases (MAPKs); Extracellular signal-regulated kinase (ERK)
资金
- National Natural Science Foundation of China [81300130]
- Reform of the Key Clinical Departments of Diagnosis and Treatment Capacity Building Projects of Provincial Hospital in Liaoning [LNCCC-D06-2015]
- Specialized Research Fund for the Doctoral Program of Higher Education of China (SRFDP) [20122104110001]
Objectives: To investigate the effects of lipoxin A4 (LXA4) on inflammatory responses in obesity-related glomerulopathy (ORG) mouse model and its potential mechanisms. Methods: Male C57BL/6 mice were randomly divided into 4 groups: normal, model, LXA4, and LXA4/Boc-2 groups (n=8). Mice in LXA4 group were intraperitoneally injected with LXA4 (40 ng/kg) once daily for 3 days following 12 weeks of high-fat diet (HFD) feeding. LXA4 receptor antagonist, Boc-2, was administered in LXA4/Boc-2 group prior to LXA4 treatment to block the effects of LXA4. Renal morphology and function impairment were determined. Inflammation was tested by measuring serum and mRNA levels of pro-inflammatory cytokines and chemokines. HFD-induced activation of nuclear factor-kappa B (NF-kappa B) and phosphorylation of mitogenactivated protein kinases (MAPKs) were investigated by immunohistochemistry and western blot. Results: HFD-feeding caused significant renal injury, pathological changes and inflammation in model group mice. LXA4 injection significantly alleviated HFD-induced effects on renal morphology and functions, as demonstrated by lower kidney index, glomerular diameter, 24h urine protein, urinary albumin creatinine ratio and renal histomorphology. Moreover, HFD-induced accumulation of pro-inflammatory cytokines and chemokines were obviously attenuated by LXA4 administration, so did the HFD-induced activation of NF-kappa B and ERK/p38 MAPK pathways. However, these effects were markedly abrogated by BOC-2 pretreatment. Conclusion: LXA4 significantly attenuated HFD-induced renal inflammation and injury in ORG models, and these effects may be associated with the inhibition of activation of NF-kappa B and ERK/p38 MAPK pathways. The findings of our study may shed light on LXA4 showed a potential therapeutic application in ORG.
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