Tu Sheng, Shao Anwen, Ren Lihong, Chen Tin, Yao Dingguo
Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310051, China.
Chin Med J (Engl). 2014;127(11):2121-8.
Diabetes mellitus (DM) is a common disease accompanied with a high incidence of hind limb ischemia (HLI). In recent years, numerous studies demonstrated that endothelial progenitor cells (EPCs) are involved in angiogenesis and maintenance of vascular integrity following HLI. On the other side, it has been proved that Astragalus polysaccharide (APS) could promote angiogenesis. In the present study, we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin (STZ)-induced diabetes.
Rats (n = 110) were randomly assigned to the following groups: sham group, ischemia group, APS group, EPCs group and APS+EPCs group. APS, EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction, and 6 rats were assessed by angiography at 28 days after induction of HLI, 6 rats were sacrificed at the same time point to take histological studies, biochemical tests were also performed at that point in the rest rats.
APS or EPCs treatment induced an increase, respectively, in the protein expression of vascular endothelial growth factor (VEGF) (36.61%, 61.59%), VEGF receptor-1 (VEGFR-1) (35.50%, 57.33%), VEGFR-2 (31.75%, 41.89%), Angiopoietin-1 (Ang-1) (37.57%, 64.66%) and Tie-2 (42.55%, 76.94%) (P < 0.05), after HLI injury. And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats, through elevating protein expression of VEGF (99.67%), VEGFR-1 (105.33%), VEGFR2 (72.05%), Ang-1 (114.30%) and Tie-2 (111.87%) (P < 0.05). Similarly, mRNA expression of VEGF, VEGFR-1, VEGFR2, Ang-1, Tie-2 also show similar trends as well as protein expression (P < 0.05).
APS or EPCs could enhance angiogenesis, and the combined treatment leads to better effort, at least, partially via VEGF/VEGFR and Ang-1/Tie-2 signaling pathway.
糖尿病（DM）是一种常见疾病，常伴有后肢缺血（HLI）的高发病率。近年来，大量研究表明，内皮祖细胞（EPCs）参与了HLI后的血管生成和血管完整性维持。另一方面，已证实黄芪多糖（APS）可促进血管生成。在本研究中，我们旨在评估APS和EPCs对链脲佐菌素（STZ）诱导的糖尿病大鼠股动脉结扎所致实验性HLI后增强血管生成的作用。
将110只大鼠随机分为以下几组：假手术组、缺血组、APS组、EPCs组和APS + EPCs组。在诱导HLI后肌肉注射APS、EPCs或等量的载体，在HLI诱导后28天通过血管造影评估6只大鼠，在同一时间点处死6只大鼠进行组织学研究，其余大鼠也在该时间点进行生化检测。
在HLI损伤后，APS或EPCs治疗分别使血管内皮生长因子（VEGF）（36.61%，61.59%）、VEGF受体-1（VEGFR-1）（35.50%，57.33%）、VEGFR-2（31.75%，41.89%）、血管生成素-1（Ang-1）（37.57%，64.66%）和Tie-2（42.5%，76.94%）的蛋白表达增加（P < 0.05）。APS和EPCs的联合治疗通过提高VEGF（99.67%）、VEGFR-1（105.33%）、VEGFR2（72.0%）、Ang-1（114.30%）和Tie-2（111.87%）的蛋白表达，增强了糖尿病大鼠HLI诱导后的血管生成作用（P < 0.05）。同样，VEGF、VEGFR-1、VEGFR2、Ang-1、Tie-2的mRNA表达以及蛋白表达也呈现相似趋势（P < 0.05）。
APS或EPCs均可增强血管生成，联合治疗效果更佳，至少部分是通过VEGF/VEGFR和Ang-1/Tie-2信号通路实现的。
