The protective effects of sevoflurane postconditioning mediated by SIRTl on learning and memory impairment in liemorrhagic shock and resuscitation mice / 中国药理学通报

ABSTRACT

Aim To explore the role of the silent information regulator (silent information regulation 1, SIRTl)-mediated apoptotic pathway in the protection of sevoflurane postconditioning in hippocampal neuronal injury of mice induced by hemorrhagic shock resuscitation (HSR). Methods A mouse model of HSR was established. The male C57BL/6J mice were randomly divided into; sham operation group (Sham group), HSR group (Shock group), sevoflurane treatment group (Sevo group), sevoflurane combined with SIRTl specific inhibitor treatment group (EX527 + Sevo group) and EX527 treatment group (EX527 group). The volume of cerebral infarction was detected by TTC staining method. The changes of hippocampal nerve cells in each group of mice were detected by TUNEL staining method. The learning and memory abilities were detected by Morris water maze test. The expression of SIRTl and apoptosis-related protein levels were delected by Western blot analysis. Results The latency of the model mice reaching the platform in Morris water maze test was prolonged, while the movement distance in the target quadrant was similarly reduced. Besides, the cerebral infarction volume remarkably increased. The number of TUNEL staining positive cells increased, and the expression of SIRTl and Bel-2 decreased while the pro-apoptosis protein Bax, and cleaved-caspase 3 expression level increased; sevoflurane treatment improved nerve injury in HSR. After combined treatment with sevoflurane and SIRTl inhibitor EX527, the protective effect of sevoflurane was attenuated on nerve injury in HSR. Conclusion Sevoflurane may play a protective role against hippocampal neuronal injury caused by HSR mediated by SIRTl apoptosis-related pathway.