comp-angiopoietin-1 recovers molecular biomarkers of neuropathy and improves vascularisation in sciatic nerve of obob micecomp-angiopoietin-1复苏的分子生物标志物坐骨神经的神经病变,提高vascularisation obob老鼠.pdf

COMP-Angiopoietin-1 Recovers Molecular Biomarkers of Neuropathy and Improves Vascularisation in Sciatic Nerve of ob/ob Mice 1 . 2. ¨ 1,3 1 1 Joanna Kosacka * , Marcin Nowicki , Nora Kloting , Matthias Kern , Michael Stumvoll , Ingo 2 2 ¨ 1 Bechmann , Heike Serke , Matthias Bluher 1 Department of Medicine, University of Leipzig, Leipzig, Germany, 2 Institute of Anatomy, University of Leipzig, Leipzig, Germany, 3 IFB Adiposity Disease, University of Leipzig, Leipzig, Germany Abstract Background: Leptin-deficient ob/ob mice are a model of type 2 diabetes induced peripheral neuropathy. Ob/ob mice exhibit obesity, insulin resistance, hyperglycaemia, and alterations of peripheral nerve fibres and endoneural microvessels. Here we test the hypothesis that cartilage oligomeric matrix protein (COMP)-Ang-1, a soluble and stabile form of Ang-1 which promotes angiogenesis and nerve growth, improves regeneration of nerve fibres and endoneural microvessels in ob/ob mice. Methods and Findings: COMP-Ang-1 (100 ng/ml) or NaCl were intraperitoneally (i.p.) injected into male (N = 184), 3-month old, ob/ob or ob/+ mice for 7 and 21 days. We measured expression of Nf68, GAP43, Cx32, Cx26, Cx43, and TNFa in sciatic nerves using Western blot analysis. To investigate the inflammation in sciatic nerves, numbers of macrophages and T-cells were counted after immunofluorescence staining. In ultrathin section, number of myelinated/non-mylinated nerve fibers, g- ratio, the thickness of Schwann cell basal lamina and microvessel endothelium were investigated. Endoneural microvessels were reconstructed with intracardial FITC injection. Treatme