Effects of Insulin-Like Growth Factor 1 on Muscle Atrophy and Motor Function in Rats with Brain Ischemia

Heng-Chih Chang ； Yea-Ru Yang ； Paulus S. Wang ； Chia-Hua Kuo ； Ray-Yau Wang

《The Chinese Journal of Physiology》 53卷5期 (2010/10) Pp. 337-348

https://doi.org/10.4077/CJP.2010.AMK080

並列摘要

Although insulin-like growth factor 1 (IGF 1) has been used in immobilizated muscles to prevent muscle atrophy, its effects on muscle atrophy after brain ischemia are not known. This study aimed to determine the effects of IGF 1 on preventing muscle atrophy in rats with brain ischemia. Middle cerebral artery occlusion (MCAO) was used to induce the brain ischemia. In the first part of the study, rats were assigned to sham control, ischemic control, and ischemia with different dosages of IGF 1 injection groups to determine the optimal dosage of IGF 1 on preventing muscle atrophy after brain ischemia. In the second part of the study, rats were assigned to sham control, ischemic control, ischemia with IGF 1, or with IGF 1 receptor inhibitor (AG1024) injection groups to determine the specificity of IGF 1 on preventing muscle atrophy after brain ischemia. IGF 1 or AG1024 was injected locally to calf muscles and anterior tibialis (TA) starting from one day after brain ischemia and injections were carried out every other day for 4 times. Muscle weight and myosin heavy chain (MHC) expression in both red (red gastrocnemius and soleus) and white (white gastrocnemius and TA) muscles were significantly decreased after brain ischemia. With at least moderate-dosage (200 ng/100 μl PBS) IGF 1 injection, the muscle weight and MHC protein could be restored in both red and white muscles resulting in better motor performance. However, the high-dose injection of IGF 1 (400 ng/100 μl PBS) did not result in further effects. IGF 1 increased the expression of p-Akt, but such effects were prevented by AG1024 resulting in muscle atrophy and poor motor function. In conclusion, peripheral application of IGF 1 not only prevented muscle atrophy but also enhanced motor function in rats with brain ischemia. The IGF 1-induced PI3K/Akt pathways are important for preventing muscle atrophy induced by brain ischemia.

並列關鍵字

insulin-like growth factor 1 ； muscle atrophy ； motor function ； brain ischemia

參考文獻

Tsai, Y. W.,Yang, Y. R.,Chen, G. H.,Chang, H. C.,Wang, R. Y.(2008).The time window of intermittent hypoxia intervention after middle cerebral artery occlusion.Chinese J. Physiol..51,324-328.

Cantley, L. C.(2002).The phosphoinositide 3-kinase pathway.Science.296,1655-1657.

Carmeli, E.,Reznick, A. Z.,Coleman, R.,Carmeli, V.(2000).Muscle strength and mass of lower extremities in relation to functional abilities in elderly adults.Gerontology.46,249-257.

Choe, M. A.,An, G. J.,Lee, Y. K.,Im, J. H.,Choi-Kwon, S.,Heitkemper, M.(2004).Effect of inactivity and undernutrition after acute ischemic stroke in a rat hindlimb muscle model.Nurs. Res..53,283-292.

Clarke, B. A.,Drujan, D.,Willis, M. S.,Murphy, L. O.,Corpina, R. A.,Burova, E.,Rakhilin, S. V.,Stitt, T. N.,Patterson, C.,Latres, E.,Glass, D. J.(2007).The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle.Cell Metab..6,376-385.