title: Angiogenesis effect of Astragalus polysaccharide combined with endothelial progenitor cells therapy in diabetic male rat following experimental hind limb ischemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tu
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310051, China.
authors.forename: Anwen
authors.initials: A
authors.lastname: Shao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
authors.forename: Tin
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China. Email: kejiaoke@163.com.
authors.forename: Dingguo
authors.initials: D
authors.lastname: Yao
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000628:therapy*; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D006614:Hindlimb / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D011134:Polysaccharides / Q000627:therapeutic use*; D051381:Rats
chemical_list: D011134:Polysaccharides