Background: Diabetes mellitus (DM) results in decreased muscle mass and harmful complications. Blood flow restriction (Bfr) and electrical stimulation (ES) increase muscle protein synthesis. We hypothesized that combined Bfr and low-intensity ES may be more effective in preventing diabetes-associated muscle atrophy by inhibiting the downregulation of protein synthesis-related pathways. In this study, the effects of combined Bfr and low-intensity ES on diabetes-associated muscle atrophy were investigated by evaluating advanced glycation end-products (AGEs) and receptor for AGEs (RAGE) in rats.
Methods: Twenty-four Goto-Kakizaki (GK) rats were randomly divided into four treatment groups: sedentary DM, DM + Bfr (pressure cuffs placed around the thigh), DM + ES, and DM + Bfr + ES. Six Wistar rats were used as an age-matched control. Levels of AGEs and the expression of RAGE, extracellular signal-regulated kinase (ERK), and ribosomal protein S6 (rpS6) were determined in plantaris muscles.
Results: Diabetes resulted in a loss of muscle mass and upregulation of AGEs and RAGE in the plantaris muscle compared with the control group. Treatment with Bfr and ES alone failed to attenuate diabetes-associated loss of muscle mass, and could not prevent the upregulation of AGEs. However, the combination of Bfr and ES prevented the diabetes-associated decrease in muscle mass and upregulation of AGEs. In addition, the combination treatment prevented diabetes-associated decreases in the expression of phosphorylated rpS6.
Conclusions: Combination treatment with Bfr and ES may prevent diabetes-associated muscle atrophy by upregulating inhibition of AGEs, which leads to the activation of protein synthesis.
摘要: 背景 糖尿病(DM)可导致肌肉含量减少以及有害的并发症。限制血流(blood flow restriction,Bfr)与电刺激(electrical stimulation,ES)可以增加肌肉蛋白质的合成。我们假设联合使用Bfr与低强度ES治疗可通过阻止蛋白合成相关通路的下调, 更有效地预防糖尿病相关肌肉萎缩。在这项研究中, 我们通过评估大鼠晚期糖基化终末产物(advanced glycation end-products,AGEs)与AGEs受体(RAGE),研究联合使用Bfr与低强度ES治疗对糖尿病相关肌肉萎缩的效果。 方法 24只Goto-Kakizaki(GK)大鼠被随机分为4个治疗组:不活动的DM组,DM+Bfr组(压力袖带放在大腿周围),DM+ES组以及DM+Bfr+ES组。对照组为6只年龄匹配的Wistar大鼠。测定跖肌的AGEs水平与RAGE的表达、细胞外信号调节激酶(signal-regulated kinase,ERK)以及核糖体蛋白S6(ribosomal protein S6,rpS6)。 结果 与对照组相比, 糖尿病可导致跖肌含量减少并且可上调AGEs与RAGE。单独使用Bfr或者ES治疗并不能减轻糖尿病相关肌肉含量的减少, 也不能防止AGEs的上调。然而, 联合使用Bfr与ES治疗可以防止糖尿病相关肌肉含量的减少以及AGEs的上调。另外, 联合治疗可以防止糖尿病相关的磷酸化rpS6表达下降。 结论 联合使用Bfr与ES治疗可以通过上调AGEs抑制作用, 防止糖尿病相关的肌肉萎缩, 活化蛋白质合成。.
Keywords: blood flow restriction; diabetes mellitus; electrical stimulation; 电刺激; 糖尿病; 限制血流.
© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.