Effects of recombinant human endostatin on peritoneal angiogenesis in peritoneal dialysis rats

Nephrology (Carlton). 2011 Aug;16(6):599-606. doi: 10.1111/j.1440-1797.2011.01465.x.

Abstract

Aim: To investigate the effects of recombinant human endostatin (Endostar) on peritoneum angiogenesis in a model of dialysate exposure in rats.

Methods: Forty male Sprague-Dawley rats were randomized to five groups: normal (group 1); uraemia (group 2); 4.25% peritoneal dialysate (PD) uraemic (group 3); uraemia + PD + recombinant human endostatin 10 mg/kg PD (group 4); and uraemia + PD + recombinant human endostatin 40 mg/kg PD (group 5). The uraemic rats model was established by 5/6 nephrectomy. Endostatin was administrated by s.c. injection every other day, over 28 days. After 28 days of PD fluid exposure, immunohistochemistry and reverse transcript polymerase chain reaction were used to detect protein and mRNA expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in each group. Microvessel density (MVD) was measured by immunohistochemistry.

Results: Compared with group 1, the mRNA and protein expressions of VEGF and bFGF were significantly upregulated in groups 2 and 3 (P < 0.05). Compared with group 3, the mRNA and protein expressions of VEGF and bFGF were significantly downregulated in groups 4 and 5 (P < 0.05). Compared with group 4, the mRNA and protein expressions of VEGF and bFGF were significantly downregulated in group 5 (P < 0.05). Compared with group 1, MVD was significantly upregulated in groups 2 and 3 (P < 0.05). Compared with group 3, MVD was significantly downregulated in groups 4 and 5 (P < 0.05).

Conclusion: Endostar can effectively inhibit rat peritoneum neoangiogenesis and the effect was dose-dependent.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endostatins / administration & dosage
  • Endostatins / pharmacology*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Immunohistochemistry
  • Injections, Subcutaneous
  • Male
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Microvessels / physiopathology
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology
  • Neovascularization, Pathologic / prevention & control*
  • Nephrectomy
  • Peritoneal Dialysis / adverse effects*
  • Peritoneum / blood supply*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Uremia / etiology
  • Uremia / metabolism
  • Uremia / physiopathology
  • Uremia / therapy*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Endostatins
  • RNA, Messenger
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Fibroblast Growth Factor 2
  • endostar protein