Therapeutic ultrasound treatment for the prevention of chronic kidney disease-associated muscle wasting in mice

Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound. It can help improve bone fracture repair and soft tissue healing. Our previous study found that LIPUS treatment could halt the chronic kidney disease (CKD) progression in mice; unexpectedly, we observed the improvement of CKD-reduced muscle weights by LIPUS treatment. Here, we further tested the protective potential of LIPUS on CKD-associated muscle wasting/sarcopenia using the CKD mouse models. Mouse models of both unilateral renal ischemia/reperfusion injury (IRI) with nephrectomy and adenine administration were used to induce CKD. LIPUS with condition of 3 MHz, 100 mW/cm², 20 min/day was applied to the kidney of CKD mice. LIPUS treatment significantly reversed the increased serum BUN/creatinine levels in CKD mice. LIPUS effectively prevented the decrease in grip strength, muscle weight (soleus, tibialis anterior, and gastrocnemius muscles), cross-section areas of muscle fibres, and muscular phosphorylated Akt protein expression by immunohistochemistry, and the increase in muscular atrogenes Atrogin1 and MuRF1 protein expression by immunohistochemistry in CKD mice. These results indicated that LIPUS could help improve weak muscle strength, muscle mass loss, muscle atrophy-related protein expression, and Akt inactivation. LIPUS application may be an alternative non-invasive therapeutic intervention on the management of CKD-associated muscle wasting.

低强度脉冲超声（Low-intensity pulsed ultrasound, LIPUS）是一类治疗超声，可促进骨折修复与软组织愈合。本团队既往研究发现，LIPUS干预可延缓小鼠慢性肾脏病（chronic kidney disease, CKD）的进展；更为意外的是，我们观察到LIPUS可改善慢性肾脏病所致的肌肉重量降低。本研究进一步采用两种CKD小鼠模型，探究LIPUS对CKD相关肌肉消耗/肌少症的保护作用。本研究通过单侧肾缺血再灌注损伤（unilateral renal ischemia/reperfusion injury, IRI）联合肾切除术、以及腺嘌呤给药两种方式构建CKD小鼠模型，以3 MHz、100 mW/cm²、每日20分钟的参数对CKD小鼠的肾脏区域实施LIPUS干预。结果显示，LIPUS治疗可显著逆转CKD小鼠升高的血清尿素氮（blood urea nitrogen, BUN）/肌酐水平；有效阻止了CKD小鼠握力下降、肌肉重量（比目鱼肌、胫前肌及腓肠肌）降低、肌纤维横截面积减小，同时经免疫组化检测发现，LIPUS可恢复肌肉磷酸化Akt蛋白的表达水平，并抑制肌肉萎缩相关基因Atrogin1与MuRF1的蛋白表达上调。上述结果表明，LIPUS可改善肌肉力量减弱、肌肉量丢失、肌萎缩相关蛋白表达异常以及Akt通路失活，提示LIPUS或可作为一种可选的非侵入性治疗手段，用于CKD相关肌肉消耗的临床管理。