Ghrelin Attenuates Acute Pancreatitis-Induced Lung Injury and Inhibits Substance P Expression

Objective. To investigate the effect of ghrelin administration on the severity of acute lung injury and on the production of proinflammatory cytokines and Substance P (SP) in rats with acute pancreatitis (AP). Methods: AP was induced in rats by sodium taurocholate injection through pancreaticobiliary duct. Ghrelin 20 nmol/kg was given before and after the treatment. Tumor necrosis factor-alpha, interleukin-1 beta, and -6 levels in the serum were measured using the radio-immunoassay method. Morphological signs of lung injury, pulmonary water content, microvascular permeability, and myeloperoxidase activity were measured. Meanwhile, the determination Of Pulmonary SP mRNA level and its expression were performed by reverse transcriptase polymerase chain reaction and immunohistochemistry. Results: The serum proinflammatory cytokines, Pulmonary water content, microvascular permeability, and myeloperoxidase activity were increased, and morphological damages were observed in the lung of AP rats. SP mRNA level and its expression were significantly higher in sham-operated rats (P < 0.05). Morphological damages were attenuated and serum cytokines and pulmonary parameters were reduced by pre- and posttreatment with ghrelin. Pulmonary SP expression was also significantly down-regulated by ghrelin (P < 0.05). Conclusions: Ghrelin attenuates the severity of acute lung injury induced by AP. The reduction of neutrophil sequestration, limitation of proinflammatory cytokines release, and inhibition of pulmonary SP expression may be the mechanisms involved in the therapeutic effect of ghrelin.