Synthetic RGDS peptide attenuates mechanical ventilation–induced lung injury in rats

ABSTRACT

Pulmonary inflammation is the key pathological presentation of mechanical ventilation-induced lung injury (VILI), and synthetic RGDS peptide has been suggested to attenuate pulmonary inflammation. The present study aimed to determine whether RGDS peptide has protective effects on VILI. Rats received 4 hours of high tidal volume mechanical ventilation with or without pretreatment with RGDS. Rats that were kept on spontaneous respiration served as controls. At the end of 4 hours, rats that received 4 hours of mechanical ventilation exhibited serious pulmonary pathological changes, more polymorphonulear and mononuclear leukocyte recruitment, more tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) production, higher total protein contents in the bronchoalveolar lavage fluids (BALFs) and more lung phosphorylation of integrin β3 and nuclear factor-κB inhibitor (I-κB), and increased NF-κB p65 binding activity than did the control group. Administration of RGDS peptide tended to significantly inhibit all these changes induced by mechanical ventilation. These results suggested that RGDS pretreatment might improve VILI in rats by attenuating inflammatory cascade related to integrin αVβ3 and NF-κB.

KEYWORDS :

• integrins
• lung injury
• mechanical ventilation
• RGDS
• NF-κB