Gong Guangming, Yuan Haipo, Liu Ya, Qi Luguang
Endocrinology Department, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
J Diabetes Res. 2016;2016:8076796. doi: 10.1155/2016/8076796. Epub 2016 Nov 22.
A new Chinese herbal formula called Mai Tong Formulae (MTF) has recently been used to treat lower limb macroangiopathy in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the effect of MTF on lower limb macroangiopathy in a spontaneous diabetic rat model (GK rats). We found that MTF treatment significantly reduced serum fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), IL6, and VEGF and increased serum insulin in this model. Histological and ultrastructural observations showed that MTF treatment significantly reduced vascular endothelial cell shedding and improved endothelium injuries. We further detect proteome alteration following MTF treatment. 25 differential proteins (DPs) abnormally expressed in GK rats were normalized by MTF treatment. These DPs significantly are enriched in biological processes and pathways that regulate muscle contraction and cGMP-PKG signaling pathway and so on. Additional protein-protein interaction (PPI) network analyses of the DPs showed that Fasn and Prkar2a are involved in the AMPK signaling pathway, and Gnas, Myh11, and Myh6 are involved in vascular smooth muscle contraction; these 5 DPs were validated by Western blotting. These results indicate that MTF treatment effectively treats lower limb macroangiopathy by regulating key proteins involved in AMPK signaling pathway and vascular smooth muscle contraction.
一种名为脉通方（MTF）的新型中药配方最近被用于治疗2型糖尿病（T2DM）患者的下肢大血管病变。在本研究中，我们在自发性糖尿病大鼠模型（GK大鼠）中研究了MTF对下肢大血管病变的影响。我们发现，在该模型中MTF治疗显著降低了血清空腹血糖（FBG）、甘油三酯（TG）、总胆固醇（TC）、白细胞介素6（IL6）和血管内皮生长因子（VEGF），并提高了血清胰岛素水平。组织学和超微结构观察表明，MTF治疗显著减少了血管内皮细胞脱落并改善了内皮损伤。我们进一步检测了MTF治疗后的蛋白质组变化。MTF治疗使GK大鼠中异常表达的25种差异蛋白（DPs）恢复正常。这些DPs显著富集于调节肌肉收缩和cGMP-PKG信号通路等生物学过程和途径。对DPs的额外蛋白质-蛋白质相互作用（PPI）网络分析表明，脂肪酸合酶（Fasn）和蛋白激酶A调节亚基2α（Prkar2a）参与AMPK信号通路，而鸟苷酸结合蛋白α刺激活性多肽（Gnas）、肌球蛋白重链11（Myh11）和肌球蛋白重链6（Myh6）参与血管平滑肌收缩；这5种DPs通过蛋白质免疫印迹法得到验证。这些结果表明，MTF治疗通过调节参与AMPK信号通路和血管平滑肌收缩的关键蛋白有效治疗下肢大血管病变。
