Quantificação de mastócitos envolvidos no desenvolvimento da nefropatia diabética e os efeitos da inibição do sistema Renina-Angiotensina-Aldosterona (SRAA)

Abstract

Type 1 diabetes mellitus (DM1) is a metabolic disorder characterized by high blood glucose levels resulting from insulin secretion defects. Hyperglycemia stimulates an increased production of renal renin and consequently, due the tissue action effects of Angiotensin II, there is an important mediator of the DN pathophysiological changes. Pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) has been widely studied and is proving to be an ally to DN treatment. There is evidence that mast cells, originally cells involved in allergic reactions, release a number of mediators and cytokines that are also related to DN. Wistar rats were divided into six groups: control (C) - without DM; Sham (S) without DM with dummy treatment; Diabetic control (CD) with DM; Enalapril (EN) diabetics treated with enalapril; Losartan (LO) diabetics treated with losartan; Aliskiren (AL) diabetics treated with aliskiren. After 90 days of treatment, animals were placed in metabolic cages during 24 hours for urine collection and later, blood collection for biochemical analysis and renal function. Then the kidneys were removed for morphological and histochemical studies and the animals were euthanized. Post-induction and final glycemia in diabetic animals were significantly higher than the values presented by non-diabetic animals. There were no significant changes in sodium and potassium plasma levels, but all diabetic animals showed increased plasma urea and increased kidney weight and body weight ratio (except AL) compared to C and S groups. The cortical collagen percentage was higher in CD group when compared to C and S groups, and EN group compared to S group. RAAS blockers prevented or minimized parameters changes such as areas of the renal corpuscle (EN), renal glomerulus (EN) and capsular space, also GFR (AL) and AUE (EN). Treatment with AL prevented the increase in the number of intact, degranulated and total mast cells, alteration observed in the kidneys of diabetic animals. It was found that treatment with RAAS blockers preserve renal function (AL) and reduces AUE (EN) in diabetics by minimizing some glomerular structural changes induced by DM, in addition to reducing (AL) the mast cells number in renal parenchyma, suggesting that these cells may be involved in the pathogenesis of DN.