Effects of fenofibrate on SOD3 expression in human BMECs and mouse brain microvascular tissues

DU Xiaoshan; YANG Xitong; XU Hongyang; CHEN Jianjie; WANG Guangming

doi:10.3969/j.issn.1002-266X.2017.05.002

Abstract：Objective To investigate the regulating effects of fenofibrate,the agonists of peroxisome proliferator-acti-vated receptor α(PPARα),on the superoxide dismutase 3 (SOD3)expression in human brain microvascular endothelial cells (BMECs)and mouse brain microvascular tissues as well as the possible mechanism.Methods The cultured BMECs were randomly divided into two groups,which were seperately treated with 10 μg/ml of fenofibrate and the same volume of DMSO for 12 h.Fifteen mice were divided into two groups,which were treated with 30 mg/kg fenofibrate and 10 mL/kg of 10% CMC by gavage for 7 days.The tRNA was extracted and the brain microvessel was isolated.The mRNA ex-pression levels of PPARαand SOD3 were detected by RT-PCR.We constructed a luciferase reporter plasmid pGL4 mSOD3 containing SOD3 promoter.The luciferase reporter plasmid pGL4 mu mSOD3 mutated from PPRE sequence were obtained by using the mutagenesis kit.The BMECs were transfected with pGL4 mSOD3 and pGL4 mu mSOD3 for 24 h.The cells were treated with fenofibrate at a final concentration of 10 μg/mL for 12 h in order to measure the luciferase activity.Re-sults The mRNA expression of PPARαand SOD3 was increased in the BMECs and brain microvessel after the treatment of fenofibrate (all P <0.05).The luciferase activity of pGL4 mSOD3 in BMECs treated with fenofibrate was enhanced after transfection of pGL4 mSOD3 for 24 h (P <0.05).The luciferase activity of BMECs treated with fenofibrate did not signifi-cantly change after transfection of pGL4 mu mSOD3 for 24 h (P >0.05).Conclusion The SOD3 expression in the human BMECs and mouse brain microvascular tissues is regulated by fenofibrate through activating PPARα.