ex-527 and Burns

To explore the effect of intrathecal injection of lycopene on pain facilitation, glial activation, and the SIRT1/mTOR pathway in the dorsal horn of rats with burn injury pain (BIP). Here we found that the mechanical pain threshold increased in the lycopene group compared with that of the control group, (P < 0.05). Compared with expression in the sham group, mTOR, pS6, p4EBP, GFAP, and Iba-1 decreased and SIRT1 increased in the lycopene group (P < 0.01). Glial activation in the spinal dorsal horn of BIP rats was alleviated by lycopene (P < 0.01). The SIRT1 and mTOR were mainly distributed in neurons in the spinal dorsal horn in the BIP model. Intrathecal injection of 3-MA (a mTOR agonist) or EX-527 (an inhibitor of Sirt1) partially antagonized lycopene-induced analgesia. Intrathecal injection of rapamycin (an mTOR inhibitor) or SRT1720 (an agonist of Sirt1) induced analgesia in BIP rats. 3-MA abrogated the SRT1720-induced analgesic effects. The present data indicated that the SIRT1/mTOR pathway changed in the spinal dorsal horn of BIP rats; Lycopene alleviated the pain sensitization of BIP rats by regulating the SIRT1/mTOR pathway and glial activation in the spinal dorsal horn.

Topics: Animals; Anti-Inflammatory Agents; Burns; Carbazoles; Injections, Spinal; Lycopene; Male; Pain Threshold; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Spinal Cord Dorsal Horn; TOR Serine-Threonine Kinases; Treatment Outcome

MicroRNA-199a (miR-199a) is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could upregulate miR-199a in alveolar macrophages. Downregulation of miR-199a inhibited the upregulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of proinflammatory cytokines, and the upregulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a. We further identified sirtuin 1 (SIRT1) as a direct target of miR-199a in alveolar macrophages, and the expression of SIRT1 was negatively correlated with the level of miR-199a. The protective role of miR-199a downregulation in LPS-stimulated alveolar macrophages and sepsis-induced ARDS could be attenuated by SIRT1 inhibitor. Taken together, these results indicate that downregulation of miR-199a might protect lung tissue against sepsis-induced ARDS by upregulation of SIRT1 through the suppression of excessive inflammatory responses and the inhibition of cellular apoptosis in lung tissue, suggesting its potential therapeutic effects on sepsis-induced ARDS.

Topics: 3' Untranslated Regions; Acute Lung Injury; Animals; Antagomirs; Apoptosis; Binding Sites; Burns; Carbazoles; Cytokines; Disease Models, Animal; Down-Regulation; Gene Expression Regulation, Enzymologic; Histone Deacetylase Inhibitors; Inflammation Mediators; Lung; Macrophages, Alveolar; Male; Mice, Inbred C57BL; MicroRNAs; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Distress Syndrome; Sepsis; Signal Transduction; Sirtuin 1