Análise dos efeitos renais em longo prazo do diabetes induzido durante a gestação em ratas wistar no período pós-parto

Abstract

The renin-angiotensin-aldosterone system (RAAS) is very important during pregnancy, working mainly through the angiotensin II (Ang II) that can interfere with the activation of Mitogenic-Activated Protein Kinases (MAPK) cascade. In addition, pregnancy is associated with marked increase in renal hemodynamics that may also be affected by diabetes mellitus (DM). The objectives were to evaluate the effects of DM induced in Wistar rats during pregnancy and maintained in the postpartum period on the renal expression of PCNA (Proliferating Cell Nuclear Antigen), α-SMA (Smooth Muscle Actin) and p-p38 and p-JNK MAPK as well as in studies of renal function and systolic blood pressure (SBP) in Wistar rats. For this, there were two groups (G): non-pregnant and pregnant. In the first G, the rats were divided into: G1 (non-pregnant controls rats), females that received intraperitoneal injection (ipi) of 0.9% saline solution and G2 (non-pregnant diabetic rats), females that received ipi of alloxan (100 mg/kg) diluted in 0.9% saline solution. In the second G, pregnant rats were divided into: G3 (control mothers), mothers that received ipi of 0.9% saline solution and G4 (diabetic mothers), mothers that received ipi of alloxan (100 mg/kg) diluted in 0.9% saline solution. Blood glucose was observed 2 days after induction and the animals were considered diabetic if they had blood glucose higher than or equal to 150 mg/dL. About 50 days after delivery for G3 and G4 and corresponding time for G1 and G2, the rats were subjected to indirect measurement of SBP by plethysmography and the determination of glomerular filtration rate (GFR) by creatinine clearance. Then, the animals were anesthetized and their kidneys were removed for histological, immunohistochemical and morphometric studies. The results showed that G2 and G4 animals had blood glucose levels (mg/dL) and urinary volume (mL) higher than animals from G1 and G2, even several days after DM induction. The SBP (mmHg) were not different among the groups, but there was a tendency for reduction in GFR (mL/min) from G4 when compared to the other G. There was also a significant increase in kidney weight (right and left)/body weight ratio of G4 in relation to other G. Morphometric analysis showed a reduction of total renal sectional area from G4 and an increase in G3. The glomerular area and the capsular space did not differ between G studied, but there was an augment in glomerular tuft area in G3 and G4. Quantification of the percentage of cortical collagen showed that G2 and G4 presented higher distribution, while the identification and count of mast cells did not differ between G. Regarding PCNA immunoreactivity, G3 showed increased glomerular proliferating cells, while in G4 it was decreased. On the other hand, in the tubulointerstitial (TBI) compartment cell proliferation was higher in G4. Glomerular expression of α-SMA and TBI were increased in G4 compared to other G. Immunoreaction for glomerular p-p38 expression showed a pattern similar to PCNA, with a reduction of p-p38 in G4 relative to other G. The immunoreactivity of p-JNK was higher in both the glomeruli and TBI compartment in G4 compared to G1, G2 and G3. It is concluded that the DM induced during pregnancy and maintained in the postpartum period in Wistar rats resulted in significant structural changes and moderate functional impairmet in kidney, showing that pregnancy has an enhancing effect of renal damage induced by diabetes and these alterations may be related to changes in the expression of p-p38 and p-JNK MAPK.