肾衰营养胶囊通过Pfkfb3-MCTs糖酵解途径调控CKD-PEW骨骼肌萎缩的作用及机制

蛋白质能量消耗（PEW）是慢性肾脏病（CKD）常见的并发症。骨骼肌萎缩是其主要病理表现，严重增加CKD患者死亡率。最新研究发现：糖酵解代谢调节肌卫星细胞（MuSCs）功能是PEW骨骼肌萎缩的关键机制。肾衰营养胶囊是临床治疗CKD-PEW的经验方，疗效显著。课题组最新RNA-seq结果发现，肾衰营养胶囊促进MuSCs分化改善骨骼肌萎缩，可能与Pfkfb3、MCTs等基因有关。故本课题拟明确肾衰营养胶囊疗效，构建Pfkfb3特异性敲除小鼠和Pfkfb3 AAV过表达小鼠，探究Pfkfb3介导糖酵解途径对MuSCs功能及PEW骨骼肌萎缩的影响。再通过肾衰营养胶囊和Pfkfb3抑制剂干预CKD小鼠，反向验证复方的作用靶点。最终阐明肾衰营养胶囊通过Pfkfb3-MCTs糖酵解途径调控PEW骨骼肌萎缩的作用机制。为骨骼肌萎缩机制发掘新的突破口，也为证明中医药良好临床疗效提供可靠的科学依据。

Protein energy expenditure (PEW) is a common complication of chronic kidney disease (CKD). Skeletal muscle atrophy is the main pathological manifestation, which affects the long-term prognosis and mortality of CKD patients. The latest research found that glycolytic metabolism regulating muscle satellite cell (MuSCs) function is a key mechanism of skeletal muscle regeneration in PEW. Protein energy expenditure (PEW) is a common complication of chronic kidney disease (CKD). Skeletal muscle atrophy is the main pathological manifestation, and it will seriously increase the mortality of CKD patients. The latest research found that glycolytic metabolism regulating muscle satellite cell (MuSCs) function is the key mechanism of skeletal muscle atrophy in PEW. Shenshuai Nutrition Capsule is an effective empirical prescription for clinical treatment of CKD-PEW. Our lasted RNA-seq result found that Shenshuai Nutrition Capsule can promote the differentiation of MuSCs and alleviate skeletal muscle atrophy in PEW, which may be related to the level of metabolic genes such as Pfkfb3 and MCTs. Therefore, Pfkfb3 skeletal muscle-specific knockout and Pfkfb3 AAV overexpressed mice are constructed to investigate the effect and mechanism of Pkfb3-MCTs metabolic pathway on PEW skeletal muscle regeneration. Besides, Shenshuai Nutrition Capsule and Pfkfb3 inhibitor are used in CKD mice to verify the target genes. Finally, it is clarified that the Pfkfb3-MCTs glycolysis pathway is the mechanism of the Shenshuai Nutrition Capsules in PEW muscle regeneration. The research is a new breakthrough in the mechanism of skeletal muscle atrophy, and it provides a reliable scientific basis for proving the good clinical efficacy of Chinese medicine.