Rosiglitazone pretreatment influences expression of PPARγ, Nrf2 and HO-1 in thrombin-activated microglia / 中国病理生理杂志

ABSTRACT

AIM:To observe the effect of rosiglitazone (RGZ) pretreatment on the expression of peroxisome proliferator-activated receptor γ( PPARγ) , nuclear factor E2-related factor 2 ( Nrf2 ) and heme oxygenase-1 ( HO-1 ) in the microglia cells activated by thrombin.METHODS:Microglia cells were obtained from the brain tissues of the newborn rats and were primarily cultured in vitro.After cultured for 14 d, the microglia cells were used in the experiment.The iso-lated microglia cells were randomly divided into normal control group, thrombin stimulation group ( TH group) , rosiglita-zone intervention group ( RGZ +TH group ) and retinoic acid intervention group ( RA +TH group ) .The expression of PPARγ, Nrf2 and HO-1 was observed by immunocytochemistry, real-time PCR and Western blot.RESULTS:The number of positive staining cells of PPARγ, Nrf2 and HO-1 in TH group, RGZ+TH group and RA+TH group were increased re-markably as compared with control group.The significant increases in PPARγ, Nrf2 and HO-1 were observed in RGZ+TH group compared with other groups.The mRNA expression of PPARγ, Nrf2 and HO-1 in RGZ+TH group was increased significantly as compared with TH group, control group or RA+TH group (P<0.01), Besides, the mRNA expression of Nrf2 and HO-1 in RA+TH group was decreased as compared with TH group or RGZ+TH group (P<0.01).The protein levels of PPARγ, Nrf2 and HO-1 in RGZ+TH group were significantly increased as compared with TH group, control group or RA+TH group (P<0.01).The protein expression of Nrf2 and HO-1 in RA+TH group was decreased as com-pared with TH group or RGZ+TH group (P<0.01).CONCLUSION:Rosiglitazone pretreatment might increase the ex-pression of PPARγ, Nrf2 and HO-1 in the microglia cells activated by thrombin.By inhibiting the expression of Nrf2 after RA pretreatment, the expression of the downstream gene HO-1 is also influenced.The anti-oxidative stress effects of rosigli-tazone might be achieved partly by modulating Nrf2 to control the downstream gene HO-1.