STY39, a Novel Alpha-Melanocyte-stimulating Hormone Analogue, Reduces Acute Lung Injury in Rats with Hemorrhagic Shock and Endotoxin Challenge

摘要

Acute lung injury (ALI) occurs as a result of a complex cascade of local and systemic events initiated by either infectious or noninfectious inflammatory stimuli. Alpha-melanocyte-stimulating hormone (a-MSH) is an endogenous tridecaneuropeptide derived from proopiomelanocortin (POMC). Although a-MSH is well known for its influence on pigmentation, it also exhibits potent antipyretic, antimicrobial, anti-inflammatory,and immunomodulatory activities. STY39, a novel a-MSH analogue designed and synthesized by our laboratory, has recently shown potent anti-inflammatory effects and inhibitory activity on bleomycin-induced experimental pulmonary fibrosis in mice. In the present study, we evaluated the effects of the new analogue on ALI in a "two-hit" rat model of resuscitated hemorrhagic shock followed by intratracheal instillation of lipopolysaccharide (LPS).