Effects of CP154526,the corticotropin releasing hormone receptor 1 antagonist,on rat hippocampal neuron apoptosis / 中国药理学通报

ABSTRACT

Aim To investigate the effects of CP1 54526,a corticotropin releasing hormone (CRH) receptor 1 antagonist,on the hippocampal neuron ap-optosis.Methods Rat hippocampal neurons were primarily cultured.Cell viability was estimated using MTT assays.Neurons were randomly divided into four groupsNormal cultures (Control);CRH-exposed cul-tures (CRH);CRH and CP1 54526 co-exposed cul-tures (CRH + CP ); CP1 54526-exposed cultures (CP).Cell apoptosis was examined by TUNEL or flow cytometry Annexin Ⅴ-PI staining.The protein levels of Bax,Bcl-2 and Caspase-3 were investigated by West-ern Blotting.Results 1 0 -8 mol·L -1 CRH decreased cell viability of cultured hippocampal neuron (P <0.05),while 50 mmol ·L -1 CP1 54526 significantly increased neuron viability (P <0.05).Compared with Control group,cell apoptotic rate,the ratio of Bax and Bcl-2 and the protein level of Caspase-3 were elevated in hippocampal neuron induced by CRH.Combined with CP1 54526 reversed the effects of CRH.Applica-tion of CP1 54526 alone had no obvious effects on cell apoptosis.Conclusions A certain concentration of CRH can induce hippocampal neuron apoptosis,and its receptor 1 antagonist CP1 54526 can effectively re-duce the apoptosis and play a neuroprotective role.