Abstract PR151

Abstract

Background & Objectives: Dexmedetomidine(Dex), an a2-adrenoceptor agonis, has been reported to be neuroprotective against ischemia-reperfusion injury, although the underlying mechanisms have not been clearly defined. The purpose of this study was to investigate the different concentration Dexmedetomidine’s influence on oxygen glucose deprivation/reperfusion(OGD / R) model of SH-SY5Y cell line and whether endoplasmic reticulum(ER) stress was involved in the neuroprotection of Dex. Materials & Methods: SH-SY5Y cells were differentiated with 10 μM ATRA for 3 days followed by 80 nM TPA for another 3 days. Differentiated SH-SY5Y cells by sequential ATRA and TPA-induced were divided into the control group(Group C) and Dex group. The Dex group consists of five subgroups: Group 0.1μM Dex, Group 1μM Dex, Group 10μM Dex, Group 100μM Dex, Group 1000μM Dex. The Dex group was treated with before-mentioned different concentration Dex at the same time of OGD. After OGD12h of Group C and Dex group, the groups were induced by reperfusion(R)12h. Then the cell viability was evaluated by the method of MTT. The cellular apoptosis was observed by Flow Cytometry method. The endoplasmic reticulum stress-related proteins were detected by Western Blot method. Results: Compared with Group C, Only Group 10μM had a neuroprotective effect, significantly increased the cell viability (p<0.001) and reduced the apoptosis (p<0.001). To explore the relationship between Dexmedetomidine and endoplasmic reticulum stress, compared with other groups (including Group C), Group 10μM up-regulated BIP and eIF2α. Further study found that Group 10μM also up-regulated MANF(Mesencephalic astrocyte-derived neurotrophic factor,an ER stress-inducible protein) and inhibited up-regulation of ATF4,caspase-3 and CHOP between Group C and Group 10μM. Meanwhile,the levels of XBP1s and ATF6 were no difference.Conclusion: These data suggest that different concentration Dex have different influence on OGD /R model of SH-SY5Y cell and only Group 10μM Dex can increase cell viability and reduce the apoptosis. Our results also indicate that BIP-eIF2α-ATF4-CHOP signaling of ER stress and MANF are associated with the neuroprotection of Dex. Disclosure of Interest: None declared