基于Myostatin调节的肌细胞蛋白质代谢研究黄芪保护腹膜功能的机理

蛋白质能量消耗累及骨骼肌消耗和腹膜功能损伤，与腹膜透析预后密切相关，改善肌细胞损伤可能减轻腹膜纤维化（PF）以保护腹膜功能。肌生成抑制素（Myostatin）调节的肌细胞蛋白质代谢在此过程中发挥关键作用，受到miRNAs的分子调控。前期研究提示黄芪可多靶点协同阻抑PF，并发现改善肌细胞损伤能减轻肾纤维化。预实验结果显示，高糖干预上调了骨骼肌与腹膜Myostatin表达并部分抑制腹膜蛋白质合成功能，提示Myostatin及蛋白质代谢参与调控PF。因此提出科研假说：黄芪可能通过miR-27靶向抑制Myostatin及其调节的肌细胞蛋白质分解，减轻肌细胞损伤，拮抗PF从而发挥腹膜功能保护作用。本研究拟在既往工作基础上，借助动物/细胞模型，利用DiR-Lamp2b载体重组miR-27由骨骼肌靶向传递至腹膜等技术，阐释维持蛋白质代谢平衡、改善肌细胞损伤在PF中的作用，揭示黄芪保护腹膜功能的新机制。

It is confirmed that muscle wasting and peritoneum dysfunction are complicated by protein-energy wasting，leading to failure of peritoneal dialysis. Improvement of skeletal muscle cells injury might be supposed to inhibit peritoneal fibrosis (PF) and protect peritoneum function. In this process, Myostatin-mediated protein turnover of skeletal muscle cells plays a crucial role, which can be regulated by miRNAs. Our previous study illustrated anti-PF effects of Astragalus. As well, we showed muscle wasting could accelerate renal fibrosis. Preliminary study found Myostatin and protein turnover could regulate PF, which associated with expression of Myostatin and protein synthesis. Therefore, we hypothesize that skeletal muscle cells injury plays a key role in peritoneum function, while Astragalus could ameliorate PF via repressing Myostatin-mediated protein degradation with miR-27. In this study, we intend to construct targeted peritoneum DiR-Lamp2b carried miR-27 mimic, clarifying effect of normal protein turnover and improvement of skeletal muscle cells injury on PF. This study may reveal new mechanism of Astragalus on peritoneum function protection.