Effects of pioglitazone on cognitive impairments induced by isoflurane anesthesia in aged mice / 中国病理生理杂志

ABSTRACT

AIM: To investigate the effects of pioglitazone , a peroxisome proliferator-activated receptor γ( PPARγ) agonist, on the cognitive impairments and inflammatory cytokine production induced by isoflurane in aged mice . METHODS:Male C57BL/6J mice ( 11-month-old, n =136 ) were assigned randomly into 5 groups control group ( Con) , isoflurane group ( Iso) , 10 mg/kg pioglitazone +isoflurane group ( Pi10+Iso) , 20 mg/kg pioglitazone +isoflu-rane group (Pi20+Iso) and 20 mg/kg pioglitazone alone group (Pi20).The mice in all isoflurane-treated groups were ex-posed to oxygen mixed with 1.4%isoflurane for 2 h.The mice in Con group and in Pi20 group were exposed to oxygen only for 2 h.Pioglitazone was suspended in 1% carboxymethyl cellulose (CMC).Pioglitazone (10 mg/kg or 20 mg/kg) was gavaged 2 h prior to the exposure of isoflurane or oxygen alone .The same volume of 1% CMC was gavaged in Con group and in Iso group.Fear conditioning tests were performed to determine the learning and memory abilities 48 h after isoflurane exposure.Fresh cerebral cortice and hippocampi were dissected to measure the protein expression of PPAR γby Western blotting, and the contents of IL-1βand TNF-αwere analyzed by ELISA 6 h after isoflurane exposure .RESULTS: Com-pared with Con group, the response of freezing behavior decreased (P0.05) in Pi10+Iso group, but the response of freezing behavior and PPARγpro-tein expression level increased significantly (P0.05).CONCLUSION:Pioglitazone attenuates cognitive impair-ments and the elevates the level of IL-1βin the hippocampus induced by isoflurane in aged mice .