hirudin and Diabetic-Angiopathies

Kidney is the most common location of microangiopathy in diabetic patients, and we designed this study to investigate the effects of hirudin on renal microangiopathy in STZ-induced diabetes rats and in vitro.. We established a diabetes model by intraperitoneal injection of STZ and administered hirudin daily by subcutaneous injection. HE staining was used to assess kidney pathological changes. Western blot and immunochemistry was used to detect the protein expression. Glomerular endothelial cells (GEC) in normal rats were assessed by cell scratch test for migration ability and tubule formation experiment for angiogenesis ability.. Compared with DN rats without any treatment, the serum creatinine, serum Cys C, 24-hour urine protein of DN rats with hirudin treatment were significantly decrease, the kidney/body weight and glomerular area of DN rats with hirudin treatment were all significantly decrease, and also significant improvement in renal pathology revealed by HE staining in DN rats after treating with hirudin. Moreover, we also found that hirudin coun not only significantly increase the prothrombin time and aivated partial thromboplastin time in DN rats, but also significantly decrease the expression of VEGF and TM-1 protein in kidney tissues of DN rats. In vitro, we found that high glucose could promote the migration and angiogensis of GEC, and significantly increased the expression of VEGF and Ang protein, but significantly decreased the expression of THBS1 and Arg1 protein. More importantly was that hirudin could inhibit the migration and angiogensis of GEC, and reversed HG-induced the expression of VEGF, Ang, THBS1 and Arg1 protein in GEC. In addition, we also found that hirudin could not only decrease HG-enhanced the activity of RhoA in GEC, but also decrease HG-enhanced the expression of p-MYPT1/MYPT1, p-p38/p38 protein in GEC.. Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes, and might be related to hirudin inhibiting glomerular endothelial cell migration and angiogenesis through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway.

Topics: Animals; Cell Movement; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Nephropathies; Endothelial Cells; Female; Glucose; Hirudins; Kidney Glomerulus; Male; Neovascularization, Pathologic; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; Signal Transduction

Topics: Adrenal Gland Diseases; Aged; Anticoagulants; Atrial Fibrillation; Diabetic Angiopathies; Hemorrhage; Heparin; Hirudins; Humans; Hydrocortisone; Hypotension; Male; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Treatment Outcome; Vasoconstrictor Agents

Bivalent direct thrombin inhibitors reduce ischemic risk compared to heparin. Results from randomized, double-blind clinical trials have demonstrated that bivalirudin is superior to heparin alone and as effective as heparin plus routine glycoprotein (GP) IIb/IIIa therapy for the prevention of ischemic events with a statistically significant reduction in the rate of in-hospital major bleeding.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Antithrombins; Clinical Trials as Topic; Coronary Disease; Costs and Cost Analysis; Diabetic Angiopathies; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Risk Assessment; Treatment Outcome