Tratamento com inibidor da Rho quinase em cobais com inflamação pulmonar alérgica crônica: modulação da inflamação eosinofílica, da expressão de citocinas inflamatórias, da matriz extracelular e do estresse oxidativo no parênquima pulmonar / Treatment with Rho-kinase inhibitor in guinea pigs with chronic allergic inflammation: modulation of eosinophilic inflammation, expression of inflammatory cytokines, extracellular matrix and oxidative stress in lung tissue

AUTOR(ES)

Renato Fraga Righetti

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

18/12/2012

RESUMO

RATIONALE: Previous studies with Rho-kinase inhibitors suggest a beneficial influence of these drugs in asthma. The relevance of distal lung tissue in functional asthmatic impairment has been intensely emphasized. There have not been any previous studies evaluating the effects of these inhibitors on the modulation of distal lung mechanics and histopathological alterations in an animal model of chronic pulmonary inflammation. OBJECTIVE: To evaluate if Rho-kinase inhibition (Y- 27632) modulates distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs with chronic allergic inflammation. METHODS: Guinea pigs received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) over 4 wk. From the 5th inhalation, the Rho-kinase group animals were submitted to Y-27632 inhalation 10 min before each inhalation with OVA or SAL. Seventy-two hours after the seventh inhalation, the animals were anesthetized and exsanguinated, and oscillatory mechanics of the lung tissue strips were performed under the baseline condition and after the ovalbumin challenge (0.1%). Afterwards, the lung slices were submitted to morphometry. RESULTS: The Rho-kinase inhibition in the ovalbumin-exposed animals attenuated the tissue elastance and resistance, eosinophils, the IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-, IFN-g, NF-kB, iNOS-positive cells and the 8-iso-PGF2, elastic, collagen and actin content compared with the OVA group (P<0.05). CONCLUSION: Rho-kinase inhibition contributes to the control of distal lung responsiveness and the eosinophilic and Th1/Th2 responses to the control of extracellular matrix remodeling in an animal model of chronic allergic inflammation. It may be considered a future pharmacological tool for the treatment of chronic pulmonary diseases.

ASSUNTO(S)

asma asthma cobaias guinea pigs inflamação pulmonar pneumonia quinases associadas a rho rho-associated kinases

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