Zeng Yao-Chi, Peng Li-Sheng, Zou Liyuan, Huang Shu-Fen, Xie Yi, Mu Gui-Ping, Zeng Xue-Hui, Zhou Xi-Lin, Zeng Ya-Chi
Department of Clinical Nutrition, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China.
Department of Science and education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China.
Biomed Pharmacother. 2017 Aug;92:86-94. doi: 10.1016/j.biopha.2017.05.018. Epub 2017 May 19.
Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear. To investigate the effect of Lyc on EPCs, we isolated EPCs from DM rat bone marrow and determined cell proliferation, cell cycle,apoptosis and autophagy of EPCs. The present study showed that 10μg/mL Lyc improved cell proliferation and had low cytotoxicity in the presence of AGEs. In addition, Lyc rescued S phase of the cell cycle arrest, reduced apoptosis rate and decreased autophagic reaction including ROS and mitochondrial membrane potential (MMP) of EPCs. Moreover, Lyc combined use of autophagy inhibitors, 3-MA, had better protective effects. Taken together, our data suggests that Lyc promotes EPCs survival and protect EPCs from apoptosis and oxidative autophagy induced by AGEs, further remaining the number and function of EPCs. This study provides new insights into Lyc protective mechanism of AGEs-induced oxidative autophagy in EPCs from DM patients and offers a new therapy for DM vascular complications.
内皮祖细胞（EPCs）广泛存在于骨髓和外周血中，参与受损血管内皮的修复和血管生成，这对患有血管并发症的糖尿病（DM）患者很重要。EPCs的数量和功能与DM患者体内产生的晚期糖基化终产物（AGEs）有关。番茄红素（Lyc）是一种已被确认的天然抗氧化剂，可保护处于AGEs微环境中的EPCs免受损伤。然而，其潜在机制仍不清楚。为了研究Lyc对EPCs的影响，我们从DM大鼠骨髓中分离出EPCs，并测定了EPCs的细胞增殖、细胞周期、凋亡和自噬情况。本研究表明，10μg/mL的Lyc在存在AGEs的情况下可改善细胞增殖且细胞毒性较低。此外，Lyc挽救了细胞周期停滞的S期，降低了凋亡率，并减少了EPCs的自噬反应，包括活性氧（ROS）和线粒体膜电位（MMP）。而且，Lyc与自噬抑制剂3-MA联合使用具有更好的保护作用。综上所述，我们的数据表明，Lyc可促进EPCs存活，并保护EPCs免受AGEs诱导的凋亡和氧化自噬，从而维持EPCs的数量和功能。本研究为Lyc对DM患者EPCs中AGEs诱导的氧化自噬的保护机制提供了新的见解，并为DM血管并发症提供了一种新的治疗方法。
