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

Abstract

Oxidative stress serves an important role in hypertensive brain damage. Peroxisome proliferator‑activated receptor γ (PPAR‑γ) 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‑γ, inducible nitric oxide synthase (iNOS), gp47phox, 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‑γ expression, increased SBP, increased ratio of activated astrocytes and TUNEL‑positive cells, increased expression of iNOS, gp47phox, caspase‑3 and Bax. Rosiglitazone administration increased Bcl‑2 and PPAR‑γ expression, decreased the ratio of activated astrocytes and TUNEL‑positive cells, decreased iNOS, gp47phox, 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.