Rosiglitazone attenuates cell apoptosis through antioxidative and anti-apoptotic pathways in the hippocampi of spontaneously hypertensive rats

Oxidative stress serves an important role in hypertensive brain damage. Peroxisome proliferator-activated receptor (PPAR-) agonists possess antioxidative and anti-apoptotic effects. The present study verified the possibility that rosiglitazone serves a neuroprotective role by alleviating oxidative stress and cell apoptosis in the hippocampi of spontaneously hypertensive rats (SHRs). SHRs and age-matched Wistar-Kyoto (WKY; both 56 weeks old) rats received gavage administration of vehicle or rosiglitazone (5 mg/kg/day) for eight weeks. Systolic blood pressure (SBP) was measured by the indirect tail-cuff method. The expression ratio of activated astrocytes was analyzed by glial fibrillary acidic protein immunohistochemistry. PPAR-, inducible nitric oxide synthase (iNOS), gp47(phox), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 expression were investigated by quantitative polymerase chain reaction and western blot analysis. The number of apoptotic cells in the hippocampus of four groups was detected using the terminal deoxynucleotidyl transferase-mediated dUTP end-labeling (TUNEL) method. Compared with the WKY group, the SHR group exhibited decreased Bcl-2 and PPAR- expression, increased SBP, increased ratio of activated astrocytes and TUNEL-positive cells, increased expression of iNOS, gp47(phox), caspase-3 and Bax. Rosiglitazone administration increased Bcl-2 and PPAR- expression, decreased the ratio of activated astrocytes and TUNEL-positive cells, decreased iNOS, gp47(phox), caspase-3 and Bax expression in the hippocampi of SHRs. However, rosiglitazone did not significantly decreased SBP in the SHR group. Therefore, rosiglitazone exerts neuroprotective effect through antioxidative and anti-apoptotic pathways, which was independent of blood pressure control.