RESUMO
BACKGROUND/AIMS: intensive insulin therapy may reduce renal dysfunction during severe illness in adult patients. We evaluated the effects of insulin-glucose (IG) in normoglycemic rats subjected to ischemia-reperfusion (I/R)-induced acute kidney injury. METHODS: animals received intravenous infusions of 5% glucose [control (C)] or IG for 96 h. I/R was induced by means of bilateral renal artery clamping for 45 min. Serum creatinine (sCr) and urea (sUr) levels were evaluated before and up to 72 h after injury. Tissue samples were evaluated 72 h after I/R on a scale of 0 (normal) to 4 (above 75%) in relation to the extent of kidney injury. RESULTS: after 48 h of I/R, sCr and sUr were increased 2- to 4-fold in C as compared to sham-operated controls (p < 0.05). IG produced significant improvements in renal function (p < 0.05). Upon histopathological analysis, the IG group presented less tubular damage in comparison to the C group: level 1, 60 versus 20%; level 2, 20 versus 30%; level 3, 20 versus 30%, and level 4, 0 versus 20%, respectively (n = 10; p = 0.057). CONCLUSION: our results suggest that IG infusion attenuates the renal damage induced by severe I/R independently of blood glucose control. This strategy may constitute a therapeutic option for the prevention and treatment of ischemic renal injury.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Glucose/uso terapêutico , Insulina/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Animais , Creatinina/sangue , Glucose/administração & dosagem , Insulina/administração & dosagem , Rim/patologia , Rim/fisiopatologia , Masculino , Modelos Animais , Ratos , Ratos Wistar , Ureia/sangueRESUMO
Recent reports highlight the importance of BMP in the vasculature. We investigated the expression pattern and role of the BMP antagonist gremlin in VSMC. We detected gremlin mRNA constitutive expression in adult and embryonic rat aortic VSMC, and in rat carotids. In vitro analysis demonstrated that angiotensin II, TGF-beta1 and PDGF induced significant changes in gremlin mRNA expression. Gremlin stable overexpression in A7r5 cells blocked BMP signaling. BMP-induced reduction in VSMC DNA synthesis was markedly inhibited by gremlin overexpression. In fact, gremlin overexpression increased DNA synthesis and cell counts, and accelerated cell cycle progression of VSMC, through mechanisms that include p27(kip1) down-regulation. Gremlin also led to marked increments in VSMC migration. In addition, gremlin gene silencing promoted a significant blockade on cell proliferation and migration. In vivo studies disclosed increased gremlin protein expression in the neointima of balloon-injured carotid arteries. In summary, the BMP antagonist gremlin is constitutively expressed in the normal vasculature. Gremlin induces VSMC proliferation and migration and is significantly regulated by growth factors and injury. We postulate that gremlin plays a part in the development of pathological phenotypic changes of adult VSMC.