| 研究実績の概要 |
Percutaneous cardiopulmonary support (PCPS) induced inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately leads to multiple organ failure. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. We investigated the protective effects of ghrelin against the PCPS-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male rats were subjected to PCPS for 4 hrs and randomly received vehicle (n=6) or a bolus of ghrelin (150 microgram/kg, sc, n=6). Rats were euthanized and heart, lung, liver, kidney and brain samples were harvested for histopathology. Blood samples were taken before PCPS, after 2 hrs and 4 hrs of PCPS. We measured the plasma levels of cytokines, catecholamines and organ damage markers. PCPS-induced leucocytosis with increased plasma levels of TNF-α, IL-6 indicating an inflammatory response. Ghrelin treatment attenuated organ damage and protein levels of 3-nitrotyrosine, but not the inflammatory response or catecholamine increase. Administration of ghrelin might provide an effective co-treatment for reducing widespread PCPS-induced organ injury.
Conference: Presented as a poster during the Experimental Biology Meeting (2017) in Chicago, USA.
|
| 今後の研究の推進方策 |
We investigated whether early pretreatment with one bolus of ghrelin administration prior to 4 hours of PCPS significantly improved PCPS-induced inflammation, oxidative stress and end organ damage in adult rats. Based on this first study we believe that in a small animal model prolonged contact between blood and the PCPS unit resulted in the destruction of blood cells and the activation of an inflammatory response and a progressive increase in catecholamines. Since ghrelin did reduce macrophage infiltration, oxidative stress and organ damage, based on this experience we will only use PCPS for a period of 2h in future experiments.
Acute myocardial infarction (AMI) morbidity has been strongly associated with an adverse and sustained increase in cardiac SNA, causes exacerbation of ischemic damage to cardiac tissue, and thus critically impairs the functional capacity of the heart leading to cardiogenic shock. Therefore, we will now investigate whether early pretreatment with ghrelin prior to PCPS can significantly improve cardiac function and remodeling events up to 2 weeks following AMI and whether these underlying mechanisms are associated with the suppression of sympathetic activation and inflammation. Sprague Dawley rats will be subjected to PCPS for 2 hrs only following AMI with pretreatment with either vehicle (n=10) or a bolus of ghrelin (150 microgram/kg, sc, n=10) prior to initiating PCPS. Using the same approaches as our first study we will determine if ghrelin suppresses sympathetic overactivation, inflammation and deterioration of cardiac function.
|
