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Ejercicio Físico En La Patogenia De La Artritis Inducida Por Proteoglicano En Ratón

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Ejercicio Físico En La Patogenia De La Artritis Inducida Por Proteoglicano En Ratón UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA FACULTAD DE CIENCIAS DE LA CULTURA FÍSICA SECRETARÍA DE INVESTIGACIÓN Y POSGRADO EJERCICIO FÍSICO EN LA PATOGENIA DE LA ARTRITIS INDUCIDA POR PROTEOGLICANO EN RATÓN TESIS QUE PARA OBTENER EL GRADO DE: DOCTORA EN CIENCIAS DE LA CULTURA FÍSICA PRESENTA: M. EN C. SUSANA AIDEÉ GONZÁLEZ CHÁVEZ DIRECTOR DE TESIS: DR. CÉSAR FRANCISCO PACHECO TENA CHIHUAHUA, CHIH., MÉXICO, SEPTIEMBRE DE 2017 UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA FACULTAD DE CIENCIAS DE LA CULTURA FÍSICA SECRETARÍA DE INVESTIGACIÓN Y POSGRADO El que suscribe, integrante del Núcleo Complementario del Programa de Doctorado Interinstitucional en Ciencias de la Cultura Física de la Facultad de Ciencias de la Cultura Física de la Universidad Autónoma de Chihuahua. CERTIFICA Que el presente trabajo titulado “Ejercicio físico en la patogenia de la artritis inducida por proteoglicano en ratón”, ha sido realizado bajo mi dirección en el Laboratorio de Investigación PABIOM de la Facultad de Medicina y Ciencias Biomédicas de la Universidad Autónoma de Chihuahua, por la M. en C. Susana Aideé González Chávez para optar por el grado de: DOCTORA EN CIENCIAS DE LA CULTURA FÍSICA Esta es una investigación original que ha sido realizada con rigor ético y científico, por lo que autorizo su presentación ante el grupo de sinodales correspondiente. Para los fines que haya lugar, se extiende la presente a los doce días del mes de Septiembre del dos mil diecisiete. Atentamente Dr. César Francisco Pacheco Tena Doctor en Ciencias Médicas Facultad de Medicina y Ciencias Biomédicas, UACH i UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA FACULTAD DE CIENCIAS DE LA CULTURA FÍSICA SECRETARÍA DE INVESTIGACIÓN Y POSGRADO El presente trabajo “Ejercicio físico en la patogenia de la artritis inducida por proteoglicano en ratón” realizado por la M. en C. Susana Aideé González Chávez, fue revisado por los profesores integrantes del Comité Tutorial quienes constaron y avalaron los cambios, avances y logros de esta investigación desde su inicio. Así mismo, y de conformidad con el Reglamento Interno de la Facultad de Ciencias de la Cultura Física, el Reglamento General de Estudios de Posgrado y el Reglamento General Académico de la Universidad Autónoma de Chihuahua, ha sido APROBADO para su presentación y defensa para obtener el grado de: DOCTORA EN CIENCAS DE LA CULTURA FÍSICA COMITÉ TUTORIAL Dr. César Francisco Pacheco Tena Facultad de Medicina y Ciencias Biomédicas Universidad Autónoma de Chihuahua Dra. Lidia Guillermina De León Fierro Dra. Claudia Esther Carrasco Legleu Facultad de Ciencias de la Cultura Física Facultad de Ciencias de la Cultura Física Universidad Autónoma de Chihuahua Universidad Autónoma de Chihuahua Chihuahua, México Septiembre de 2017 ii UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA FACULTAD DE CIENCIAS DE LA CULTURA FÍSICA SECRETARÍA DE INVESTIGACIÓN Y POSGRADO El contenido del presente reporte de la investigación denominada “Ejercicio físico en la patogenia de la artritis inducida por proteoglicano en ratón” realizado por la M. en C. Susana Aideé González Chávez, fue revisado y APROBADO por los profesores externos al Comité Tutorial quienes constataron su calidad para ser presentado como opción a tesis de: DOCTORADO EN CIENCAS DE LA CULTURA FÍSICA REVISORES EXTERNOS Dra. Mónica Vázquez Del Mercado Dr. Everardo González Rodríguez Espinosa Facultad de Medicina y Instituto de Investigación en Ciencias Biomédicas Reumatología y del Sistema Músculo Universidad Autónoma de Chihuahua Esquelético, Centro Universitario de Ciencias de la Salud Universidad de Guadalajara Chihuahua, México Septiembre de 2017 iii Copyright © 2017 Susana Aideé González Chávez Derechos Reservados iv RECONOCIMIENTO INSTITUCIONAL La presente investigación se realizó en el Laboratorio de Investigación: Patogenia Biomédica y Molecular (PABIOM) de la Facultad de Medicina y Ciencias Biomédicas de la Universidad Autónoma de Chihuahua durante el periodo 2014-2017. Fue parcialmente financiado con fondos propios de dicha Unidad Académica y por el Programa de Fortalecimiento de la Calidad Educativa PFCE 2016. v DEDICATORIA Con amor a mi esposo Joel y a mi pequeño hijo Leo, mis fieles compañeros de vida. Gracias por caminar a mi lado en cada momento, por su comprensión y apoyo para cumplir esta meta. Los Amo. vi AGRADECIMIENTOS A la Facultad de Medicina y Ciencias Biomédicas de la Universidad Autónoma de Chihuahua, Directivos y Administrativos, por el apoyo brindado para el desarrollo de la presente investigación. De manera especial y sincera a el Dr. César Pacheco-Tena, le agradezco la oportunidad de trabajar a su lado. Espero que sus metas de trabajo sean todas alcanzadas y que los logros PABIOM sean multiplicados. A mi compañera de hazaña, Celia Quiñonez. Gracias por tu infinita paciencia. Ya es el segundo viaje que volamos juntas. Te quiero. A el Dr. Rigoberto Marín Uribe, por su gran esfuerzo a pesar de todas las adversidades para que me fuera posible ser parte de este posgrado. Estoy infinitamente agraecida con usted. A las integrantes del comité tutorial, Dra. Claudia Carrasco y Dra. Guillermina De León por las recomendaciones aportadas a la presente investigación. A la Dra. Mónica Vázquez del Mercado y a el Dr. Everardo González Rodríguez por sus valiosas aportaciones en la revisión de la presente Tesis. A mis compañeros y amigos Omar, Jaime, Diana y Anibal, por su compañía y apoyo en este trayecto. Fue una fortuna conocerlos, segura estoy que esto solo es el comienzo de nuestras historias. A mi familia, a mis padres Maria y Jose Luis y hermanos Cecy, Roge, Luis y Miguel, por siempre estar al pendiente y apoyándome en todo lo que hago. De manera especial a Roge por la construcción de la banda sinfín que le dio sentido a esta investigación. A mi tia Soco (Coquis), quien a distancia vive cada paso en mi vida. Nadie como usted para escucharme y aconsejarme. Gracias por acompañarme en todo este proceso, fue grandioso tenerla a mi lado G R A C I A S vii ÍNDICE DEDICATORIA ..................................................................................................................... VI AGRADECIMIENTOS ......................................................................................................... VII ÍNDICE ............................................................................................................................... VIII 1.1 LISTA DE TABLAS ...................................................................................................... XII 1.2 LISTA DE FIGURAS ................................................................................................... XIII 1.3 LISTA DE ABREVIATURAS ....................................................................................... XIV RESUMEN .............................................................................................................................. 1 ABSTRACT ............................................................................................................................ 3 CAPÍTULO 1. INTRODUCCIÓN ............................................................................................. 5 1.1 MARCO TEÓRICO ............................................................................................................ 6 1.1.1 Espondiloartropatías o Espondiloartritis (Espa) ...................................................... 6 1.1.1.1 Diagnóstico y actividad de la enfermedad ....................................................... 9 1.1.1.2 Tratamiento ................................................................................................... 10 1.1.1.3 Bases genéticas ............................................................................................ 12 1.1.1.4 Patogenia ...................................................................................................... 15 1.1.1.5 Neoformación ósea en la Espa ...................................................................... 16 1.1.1.5.1 Proteínas morfogénicas óseas (BMPs) ................................................... 17 1.1.1.5.2 Señalización Wnt .................................................................................... 20 1.1.1.5.3 Señalización Hedgehog .......................................................................... 22 1.1.1.6 Estrés mecánico y neoformación ósea .......................................................... 23 1.1.2 Ejercicio como tratamiento de las Espa ................................................................ 27 1.1.2.1 Ejercicio y medidas de desenlace de la enfermedad ..................................... 29 1.1.2.2 Ejercicio y efectos cardiorrespiratorios en Espa ............................................ 36 1.1.3 Modelos animales de Espa .................................................................................. 39 1.1.3.1 Modelo de artritis inducida por proteoglicano (AIPG) en ratón ....................... 40 1.1.4 Modelo de ejercicio en ratón ................................................................................ 42 1.1.4.1 Ejercicio en banda sinfín................................................................................ 43 1.2 PLANTEAMIENTO DEL PROBLEMA ................................................................................... 44 1.3 JUSTIFICACIÓN .............................................................................................................. 47 1.4 OBJETIVOS ................................................................................................................... 49 1.4.1 Objetivo General .................................................................................................
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