Abstract
Diabetes mellitus (DM) especially type II is a major health problem and diabetic nephropathy is the main cause of end stage renal disease (ESRD). Renal ischemia/reperfusion (I/R) injury is common in diabetic patients. Recent studies reported increased vulnerability of kidney to I/R injury in diabetic rats. Mechanisms behind this increased vulnerability not fully understood. The present study investigated the effect of acute ischemia for 45 min on proinflammatory cytokines, apoptotic markers, and nitric oxide (NO) in a rat model of type II diabetes. Sixty male Sprague Dawley rats were divided into 4 groups (n = 15, each); Group I: Normal rats, Group II: Normal rats underwent left renal ischemia for 45 min, Group III: diabetic rats without renal ischemia, Group IV: diabetic rats underwent left renal ischemia for 45 min. Blood and kidney samples were taken 24 h after ischemia. Serum glucose, fructosamine, creatinine, TNFα, as well as the expression of TGFβ, NFkappaB, iNOS, survivin, and Bcl2 in kidney tissue was measured. Type II DM caused significant increase in serum glucose, fructosamine, creatinine, and TNFα and expression of TGFβ, NFkB and iNOS in renal tissue (P < 0.001). Also, DM caused significant increase in apoptotic cell death with increase in Bcl-2 expression and decreased survivin in kidney. 45 min ischemia in diabetic rats caused more significant increase in serum TNF-α and expression of TGF-β, NF-kappa B and iNOS (P < 0.001). Also; there was a positive correlation between blood glucose and TNFα, TGFβ, NFkB and iNOS with negative correlation with survivin (P < 0.01). Type II DM render the kidney more susceptible to ischemic injury. Proinflammatory cytokines TNF-α, TGFβ, and NFκB and iNOS as well as Bcl2 and survivin may contribute to the enhanced renal ischemic injury in type II DM. Also, hyperglycaemia may be involved in hypersensitivity of kidney to ischemic injury in DM. Key words: Diabetes, kidney, ischemia, apoptosis, TNFalpha, TGFbeta, NFkB, iNOS, Bcl-2, surviving.
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