Publication: Modulación mediante precondicionamiento isquémico de la respuesta inflamatoria y apoptótica inducida por isquemia-reperfusión en un modelo experimental porcino de autotrasplante pulmonar
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2018-11-20
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Universidad Complutense de Madrid
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Abstract
En diversas situaciones clínicas y quirúrgicas, cada vez más frecuentes en la actualidad, el pulmón se ve sometido a períodos de isquemia más o menos prolongados con el consiguiente riesgo de producirse un síndrome de isquemia-reperfusión (SIR). Este síndrome, implica una compleja reacción inflamatoria que cursa con una disrupción de las barreras endoteliales y epiteliales, dando lugar a edema pulmonar grave y disfunción pulmonar, que aumenta la morbimortalidad temprana postquirúrgica. Debido sus importantes consecuencias, es de gran interés el desarrollo de métodos de protección pulmonar frente al SIR.
El precondicionamiento isquémico (PCI) es un método por el cual se somete a un órgano a uno o varios períodos breves de isquemia, previo a una agresión isquémica mayor, con el fin de reducir la extensión del daño por isquemia-reperfusión. Existe poca evidencia científica de los efectos del PCI sobre el SIR pulmonar, pero ha demostrado su efecto protector en varios modelos experimentales animales. HIPOTESIS Y OBJETIVOS: Nos planteamos como hipótesis, que el PCI sobre el pulmón podría ejercer un efecto protector precoz sobre SIR, y que ésta protección puede ponerse de manifiesto en el tejido pulmonar mediante técnicas histológicas e inmunohistoquímicas (IHQ). Para intentar demostrar la hipótesis planteada, se diseñó un modelo de autotrasplante pulmonar en cerdo para el estudio del tejido pulmonar sometido a una isquemia prolongada y un breve periodo de reperfusión (30 minutos). La realización de maniobras de PCI permite valorar, como objetivo principal de este estudio, los efectos protectores sobre el SIR pulmonar. Los objetivos específicos fueron la realización de un análisis histológico del daño pulmonar (mediante tinción con hematoxilina-eosina) y análisis de expresión inmunohistoquímica de CD68 (para identificar la implicación de células de estirpe monocito-macrófago), proteína quimiotáctica de monocitos-1 (MCP-1) y proteínas relacionadas con la apoptosis como son la caspasa-9 y la proteína Bcl-2, y analizar los efectos del PCI sobre ellos...
Some clinical and surgical procedures widely used nowadays involve inducing lung ischemia for extended periods of time, with the risk of developing lung ischemia-reperfusion injury (LIRI). This syndrome involves a complex inflamatory response that causes disruption of epithelial and endothelial barriers and leads to severe pulmonary edema and lung dysfunction, thus increasing early postoperative morbidity and mortality. Given its important consequences, there is a growing interest in developing methods to protect the lung from developing LIRI. Ischemic preconditioning (IP) is a method that uses short periods of ischemia on one or more organs prior to prolonged ischemia in order to reduce the extension of the damage caused by IR. There is little evidence of the effect of IP on LIRI. However, its protective effect has been proven on some experimental animal models. HYPOTHESIS AND OBJECTIVES: Our hypothesis was that IP could have a protective effect on lung IRI, and it could be demonstrated on lung tissue by means of histologic and immunohistochemical techniques. In order to prove our hypothesis, we designed a lung autotransplantation model on pigs to evaluate lung tissue exposed to prolonged ischemia and a subsequent short-period reperfusion (30 minutes). The primary aim of this study was to evaluate the protective effect of IP maneuvers on lung IRI. The specific aims were to analyze histologic lung-tissue injury (using hematosilin-eosin staining) and immunohistochemical expression of CD68 (to identify the recruitment of cells of a monocyte/macrophage lineage), monocyte chemoattractant protein-1 (MCP-1) and apoptosis-related proteins such as caspase-9 and Bcl-2, as well as to evaluate how IP affects them...
Some clinical and surgical procedures widely used nowadays involve inducing lung ischemia for extended periods of time, with the risk of developing lung ischemia-reperfusion injury (LIRI). This syndrome involves a complex inflamatory response that causes disruption of epithelial and endothelial barriers and leads to severe pulmonary edema and lung dysfunction, thus increasing early postoperative morbidity and mortality. Given its important consequences, there is a growing interest in developing methods to protect the lung from developing LIRI. Ischemic preconditioning (IP) is a method that uses short periods of ischemia on one or more organs prior to prolonged ischemia in order to reduce the extension of the damage caused by IR. There is little evidence of the effect of IP on LIRI. However, its protective effect has been proven on some experimental animal models. HYPOTHESIS AND OBJECTIVES: Our hypothesis was that IP could have a protective effect on lung IRI, and it could be demonstrated on lung tissue by means of histologic and immunohistochemical techniques. In order to prove our hypothesis, we designed a lung autotransplantation model on pigs to evaluate lung tissue exposed to prolonged ischemia and a subsequent short-period reperfusion (30 minutes). The primary aim of this study was to evaluate the protective effect of IP maneuvers on lung IRI. The specific aims were to analyze histologic lung-tissue injury (using hematosilin-eosin staining) and immunohistochemical expression of CD68 (to identify the recruitment of cells of a monocyte/macrophage lineage), monocyte chemoattractant protein-1 (MCP-1) and apoptosis-related proteins such as caspase-9 and Bcl-2, as well as to evaluate how IP affects them...
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Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Anatomía Patológica, leída el 19/06/2017