Effect of pioglitazonc on the expression of PPARv, NF-KB c-Rl md Bcl-xL in cultmed rat cortical neurom after the oxygn-glucose/nmxygenation

Abstract

Objective To investigate the effect of pioglitazone （PIO） on the expression of peroxisome proliferators-activated receptor （PPAR/）, nuclear factor-KB （NF-Kt3） c-Re1 and anti-apoptosis factor Bcl-xL in cultured Wistar rat cortical neurons after oxygen-glucose deprivation/reoxygenation （OGD/R）. Methods The rat cerebral cortical neurons were primarily cultured in vitro and a model of OGD/R was induced. The rats were divided into 7 groups： normal, OGD 4 h/R 6 h, OGD 4 h/R 12 h, OGD 4 h/P, 6 h ＋ PIO, OGD 4 h/P, 6 h ＋ PPAR~/ inhibitor T0070907 （TIO）, OGD 4 h/R 12 h ＋ PIO, and OGD 4 h/R 12 h ＋ TIO groups. Western blot was used to detect the expression of PPAR-y and NF-KB c-Rel protein in neurons. Reverse transcription-polymerase chain reaction assay was used to detect the expression of Bcl-xL mRNA in neurons. Results Western blot analysis showed that the expression levels of PPAR/ and NF-KB c-Rel proteins after OGD/R were increased significantly compared to those of the normal group （P 〈 0. 01 ）. After giving PIO, the expression levels of PPAR/ and NF-KB c-Rel proteins were further increased, and they were significantly higher than those in the OGD 4 h/R 6 h and OGD 4 h/R 12 h groups （P 〈 0. 01）, and after giving TIO, the expression levels of PPAR＇,/ and NF-KB c-Rel proteins were decreased, and they were significantly lower than those in the OGD/R group （P 〈 0. 05） and the corresponding PIO group （P 〈 0. 01）. Reverse transcription-polymerase chain reaction analysis showed that the expression level of Bcl-xL mRNA in the OGD 4 h/R 6 h group was significantly higher than that in the normal group （P 〈0. 01）. The expression level of Bcl-xL mRNA in the P10 group was significantly higher than that in the OGD 4 h/R 6 h and OGD 4 h/R 12 h groups （P 〈0. 01）. After giving TIO, the expression of Bcl-xL mRNA was decreased. It was significantly lower than that in the OGD/R and corresponding PIO groups （P 〈 0. 05 and P 〈 0. 01 ）. Conclusions PIO can upregulate the expression of PPAR~ protein in cultured cortical neurons after OGD/R, and then increase the expression of anti-apoptotic factor Bcl-xL mRNA of NF-KB c-Rel regulation. This may be the part mechanism of PPAR/ neuroprotective effect. Key words: Pioglitazone; PPAR; Neurons; Cerebral Cortex; Brain Ischemia; Glucose; Oxygen; NF-KB; bcl-X Protein; Rats