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KMID : 0338420120270020163
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The Korean Journal of Internal Medicine
2012 Volume.27 No. 2 p.163 ~ p.170
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Phosphodiesterase Inhibitor Improves Renal Tubulointerstitial Hypoxia of the Diabetic Rat Kidney
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Sun Hui-Kyoung
Lee Yun-Mi
Han Kum-Hyun
Kim Han-Seong
Ahn Seon-Ho
Han Sang-Youb
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Abstract
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Background/Aims: Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney.
Methods: PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1α in renal tubule cells.
Results: PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1α, VEGF, and GLUT- 1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1α and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT- 1 at 4 weeks. The expression of HIF-1α protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1α protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 μM), which enhanced HIF-1α mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1α expression.
Conclusions: PTX attenuates tubular hypoxia in the diabetic kidney.
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KEYWORD
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Cell hypoxia, Diabetic nephropathies, Phosphodiesterase inhibitors
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