combined effect of ampkppar agonists and exercise training in mdx mice functional performance综合效应ampkppar受体激动剂和运动训练的mdx老鼠功能性能.pdf

Combined Effect of AMPK/PPAR Agonists and Exercise Training in mdx Mice Functional Performance ´ 1 ˜ 2 3 3 Carlos R. Bueno Junior , Lucas C. Pantaleao , Vanessa A. Voltarelli , Luiz Henrique M. Bozi , Patricia 3 1 Chakur Brum , Mayana Zatz * 1 Human Genome Research Center - Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil, 2 Department of Physiology and Biophysics - Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil, 3 School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil Abstract The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPARd agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Trea