Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure
| Autor: | Yasuhiko Ito, Kaoru Yasuda, Tokunori Yamamoto, Takenori Ozaki, Yukio Yuzawa, Momokazu Gotoh, Seiichi Matsuo, Yoshiki Morita, Shoichi Maruyama, Chabouk Anas |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_treatment Thrombomodulin Pharmacology Kidney Argatroban Rats Sprague-Dawley chemistry.chemical_compound Ischemia Medicine Animals Blood urea nitrogen Transplantation Creatinine TUNEL assay business.industry Acute Kidney Injury medicine.disease Recombinant Proteins Rats medicine.anatomical_structure chemistry Nephrology Immunology Hemodialysis business Kidney disease medicine.drug |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 23(1) |
| ISSN: | 0931-0509 |
| Popis: | Background. Thrombomodulin (TM) is an endothelial anti-coagulant cofactor which also has antiinflammatory properties. The present study was performed to investigate the effects of recombinant human soluble TM (RHS-TM) on ischaemia/reperfusion (I/R) renal injury. Methods. A right nephrectomy was performed in rats, and the left kidney was filled with RHS-TM (0.25 mg/kg), argatroban (20 mg/kg) or a vehicle for 45 min. Before reperfusion, the fluid trapped in the kidney was completely removed. At 24 h after I/R, renal cortical blood flow was measured using a CCD video camera, and the kidneys were harvested for the study. Next, cultured human umbilical vein endothelial cells were treated with RHS-TM (2, 10 or 50 mg/ml) or a vehicle, and incubated for 5 h in culture medium containing 300mM hydrogen peroxide. Apoptotic cell death was analysed by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Results. Immunohistochemistry revealed that the level of TM expression decreased in rat kidneys after I/R. RHS-TM significantly decreased blood urea nitrogen and serum creatinine levels. It also prevented a reduction in cortical blood flow, and attenuated tubular damage and macrophage/neutrophil infiltration. In addition, the number of TUNEL-positive cells decreased significantly in rats treated with RHS-TM. In contrast, argatroban, an inhibitor of thrombin did not show significant renoprotective actions. The results of in vitro study showed that RHS-TM significantly suppressed the number of apoptotic cells. Conclusion. The transient intrarenal administration of RHS-TM, but not argatroban, to the kidney attenuates I/R renal injury. The present study suggests that RHSTM would be a useful tool in preventing transplanted kidney damage or treating acute renal failure in the clinical setting. |
| Databáze: | OpenAIRE |
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