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摘要
The inflammatory response plays an important role in carbon tetrachloride (CCl4)-induced acute liver injury and methane has been shown to exert beneficial effects on inflammation-associated diseases. Thus, we investigated the potential protective effects of methane-rich saline (MS) on CCl4-induced acute liver injury and explored the underlying mechanism. A CCl4-induced acute liver injury model was established by injection of CCl4 (0.6 ml/kg, ip) in mice followed by treatment with MS (16 ml/kg, ip), 24 h later. All groups of mice were sacrificed and blood and liver tissues were collected. Serum aminotransferase, necrotic areas, and inflammatory cell infiltration in liver slices were enhanced after CCl4 treatment but decreased with MS treatment. IL-6, TNF-alpha, IL-1 beta, IFN-gamma, ICAM-1, CXCL1, MPO, NF-kappa B p65, ERK, JNK, and MAPK P38, expression in serum or liver homogenate were greater after CCl4 treatment but comparatively less after MS treatment. Only IL-10 increased after MS treatment. Anti-IL10 blockade (1.5 mg/kg) restored MS-mediated attenuated phosphorylation of NF-kappa bB/MAPK and the protective effect of MS was abolished for all indices examined. The PI3K inhibitor, wortmannin had the same effects on MS as anti-IL-10 antibody. MS also induced phosphorylation of GSK-3 beta and AKT in CCl4-treated mice. After pre-treatment with wortmannin (0.7 mg/kg), phosphorylation of GSK-3 beta and AKT proteins were reduced compared to its solvent control group-DMSO-treated animals. Thus, the data provide evidence that MS may activate the PI3K-AKT-GSK-3 beta pathway to induce IL-10 expression and produce anti-inflammatory effects via the NF-kappa B and MAPK pathways. The findings provide a new pharmacological strategy for management of inflammatory response after acute liver injury.
- 出版日期2017-8
- 单位中国人民解放军第二军医大学; 中国人民解放军南京军区福州总医院
