Zhang Jinbao, Zhuang Pengwei, Wang Yan, Song Lili, Zhang Mixia, Lu Zhiqiang, Zhang Lu, Wang Jing, Alemu Paulos N, Zhang Yanjun, Wei Hongjun, Li Hongyan
Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
PLoS One. 2014 Jun 26;9(6):e100918. doi: 10.1371/journal.pone.0100918. eCollection 2014.
Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB) is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes) and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD) feeding plus streptozotocin (STZ) injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1) and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p-) of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.
骨骼肌萎缩是糖尿病的严重并发症之一。知母-黄柏药对（ZB）在治疗消渴（即糖尿病）及其并发症的中药方剂中广泛应用。然而，ZB对肌肉萎缩逆转的作用及其潜在机制仍不清楚。在本研究中，我们探究了ZB对糖尿病小鼠骨骼肌萎缩的作用及可能机制。通过高脂饮食（HFD）喂养加链脲佐菌素（STZ）注射建立糖尿病肌肉萎缩动物模型。口服ZB 6周后，采用生化、组织学和蛋白质印迹法评估ZB对肌肉萎缩逆转的作用及其潜在机制。ZB治疗显著增加了糖尿病小鼠的骨骼肌重量、力量和横截面积。生化结果显示，与未治疗的糖尿病组相比，ZB治疗降低了血糖水平，并显著提高了血清胰岛素样生长因子1（IGF-1）和胰岛素水平。蛋白质印迹结果显示，与模型组相比，ZB激活了mTOR信号通路，表现为Akt、mTOR、Raptor、S6K1的磷酸化（p-）增加，Foxo3表达降低。ZB可逆转糖尿病小鼠的肌肉萎缩。这可能是通过激活促进蛋白质合成的mTOR信号通路，以及使抑制蛋白质降解的foxo3蛋白失活来实现的。这些发现提示ZB可能被视为治疗糖尿病性肌肉萎缩的潜在候选药物。
