Chang Heng-Chih, Yang Yea-Ru, Wang Paulus S, Kuo Chia-Hua, Wang Ray-Yau
Department and Institute of Physiology, National Yang-Ming University, Taiwan, Republic of China.
Chin J Physiol. 2010 Oct 31;53(5):337-48. doi: 10.4077/cjp.2010.amk080.
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 microl 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 microl 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.
尽管胰岛素样生长因子1（IGF - 1）已被用于固定的肌肉中以预防肌肉萎缩，但其对脑缺血后肌肉萎缩的影响尚不清楚。本研究旨在确定IGF - 1对预防脑缺血大鼠肌肉萎缩的作用。采用大脑中动脉闭塞（MCAO）诱导脑缺血。在研究的第一部分，将大鼠分为假手术对照组、缺血对照组和不同剂量IGF - 1注射的缺血组，以确定IGF - 1预防脑缺血后肌肉萎缩的最佳剂量。在研究的第二部分，将大鼠分为假手术对照组、缺血对照组、IGF - 1注射的缺血组或IGF - 1受体抑制剂（AG1024）注射的缺血组，以确定IGF - 1预防脑缺血后肌肉萎缩的特异性。从脑缺血后一天开始，将IGF - 1或AG1024局部注射到小腿肌肉和胫前肌（TA），每隔一天注射一次，共注射4次。脑缺血后，红色肌肉（红色腓肠肌和比目鱼肌）和白色肌肉（白色腓肠肌和TA）的肌肉重量和肌球蛋白重链（MHC）表达均显著降低。至少中等剂量（200 ng/100 μl PBS）的IGF - 1注射可使红色和白色肌肉的肌肉重量和MHC蛋白恢复，从而改善运动性能。然而，高剂量注射IGF - 1（400 ng/100 μl PBS）并未产生进一步的效果。IGF - 1增加了p - Akt的表达，但AG1024可阻止这种作用，导致肌肉萎缩和运动功能不良。总之，外周应用IGF - 1不仅可预防脑缺血大鼠的肌肉萎缩，还可增强其运动功能。IGF - 1诱导的PI3K/Akt信号通路对于预防脑缺血诱导的肌肉萎缩很重要。
