Statins ameliorate glomerular permeability changes in streptozotocin-induced diabetic rats.

摘要

AIMS: Statins reduce albumin excretion rate and retard the progression of diabetic nephropathy. Whether statins alter size selectivity of glomerular filtration in diabetic rats is not known. METHODS: The creatinine clearance and the permeability of glomeruli to a group of fluorescein isothiocyanate dextrans of varying molecular weights were studied in rats with streptozotocin-induced diabetes that were treated with either 10 mg/kg rosuvastatin or simvastatin for 5 weeks. RESULTS: Statin therapy did not significantly alter the increased creatinine clearance in diabetic rats. During the 5 hours of urine collection there was near-complete filtration of 4-, 10-, and 20-kD dextrans in all rat groups studied. The filtration of 70- and 40-kD dextrans was significantly increased in diabetic rats after 5 weeks of diabetes. Rosuvastatin but not simvastatin was associated with partial normalization of glomerular filtration of the 70- and 40-kD dextrans. Treatment with mevalonate (150 mg/kg in drinking water for 5weeks) reversed the favorable effects of rosuvastatin on glomerular permeability. CONCLUSIONS: Statin treatment of rats with streptozotocin-induced diabetes ameliorates glomerular permeability changes. The favorable effect of rosuvastatin is probably related to the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, because mevalonate treatment reversed the favorable effects of rosuvastatin.