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Biomed Pharmacother ; 103: 1362-1368, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29864919

RESUMO

Sepsis, an overwhelming systemic inflammatory disease, is the leading cause of acute lung injury (ALI). Despite plenty of researches have been done, effective drugs treating septic ALI are still eagerly needed in the clinic. Dexmedetomidine (Dex), a potent alpha-2 adrenoreceptor agonist, has been reported to possess antioxidant, anti-apoptosis and anti-inflammatory abilities. Taurine, a kind of intracellular free amino acid, has been used to treat various diseases. This study aimed to explore the combination effect of Dex and Taurine on septic ALI and the underlying mechanism in vivo. The establishment of septic ALI was set up in SD rats by cecal ligation and puncture (CLP) operation. Results indicated that Dex or Taurine could reduce septic ALI-induced cell apoptosis via decreasing caspase-3 activity. However, the combination of Dex or Taurine produced greater effect. Besides that, Dex combined with Taurine could better promote cell proliferation with remarkably elevated Ki67 expression. The combination of Dex and Taurine significantly suppressed the activation of NF-κB pathway via inhibiting P65 phosphorylation and P65 nuclear translocation, leading to the down-regulation of interleukin (IL)-6 and IL-1ß. Moreover, co-administration of Dex and Taurine alleviated the imbalance of Th1/Th2 induced by septic ALI to a great extent. All in all, our study suggested the synergistic therapeutic effect of Dex and Taurine on septic ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Dexmedetomidina/uso terapêutico , Sistema Imunitário/patologia , Substâncias Protetoras/uso terapêutico , Sepse/complicações , Taurina/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Dexmedetomidina/administração & dosagem , Dexmedetomidina/química , Sistema Imunitário/efeitos dos fármacos , Inflamação/patologia , Antígeno Ki-67/metabolismo , NF-kappa B/metabolismo , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Sepse/patologia , Transdução de Sinais/efeitos dos fármacos , Taurina/administração & dosagem , Taurina/química , Taurina/farmacologia
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