ABSTRACT
OBJECTIVE: To investigate the effects of dexmedetomidine(Dex) preconditioning on neuroapoptosis in hippocampus induced by isoflurane and the expression of CRMP2 proteins in neonatal rats. METHODS: Sixty neonatal rats at postnatal day 7 were assigned randomly into control group, Dex preconditioning control group, isoflurane group and isoflurane with Dex preconditioning groups which at dose of 25, 50 and 75 μg·kg-1. Rats in groups of isoflurane or control were exposed 0.75% isoflurane or air for 6 h. Rats in groups of Dex preconditioning were injected intraperitoneally with different doses of Dex 20 min before exposure and rats in other groups were injected intraperitoneally with 150 μL saline. At the end of exposure, the hippocampus of some rats were separated and proteins expression of cleaved caspase-3, phospho-CRMP2 (p-CRMP2), CRMP2 were detected by Western blot (n=6); other rats were perfused and their brains were embedded by paraffin, the neuronal apoptosis in hippocampus CA1 was detected by TUNEL staining 2 h after exposure (n=4). RESULTS: The number of TUNEL positive cells in hippocampus CA1 of rats in isoflurane group was increased by 434.99% (P<0.001) when compared with control group, Dex at dose of 75 μg·kg-1 significantly inhibited the increase of isoflurane-induced TUNEL positive cells by 71.87% (P<0.001). The expression of cleaved caspase-3 protein in isoflurane group increased by 90.20% (P<0.001) compared with control group, while Dex at dose of 25, 50 and 75 μg·kg-1 reversed isoflurane-induced increase of cleaved caspase-3 by 30.54% and 53.71%(P<0.05)and 96.71% (P<0.001)separately. Isoflurane increase the ratio of p-CRMP2/CRMP2 in the hippocampus by 119.41% (P<0.001), and didn't influence the expression of CRMP2; while Dex at dose of 50 and 75 μg·kg-1 inhibited isoflurane-induced increase of p-CRMP2/CRMP2 ratio by 63.75% (P<0.01) and 77.70% (P<0.01) and increased the expression of CRMP2 by 44.30% (P<0.05) and 62.13% (P<0.01). CONCLUSION: Dex Attenuates isoflurane-induced neurodegeneration through inhibitory effect of hippocampal neuroapoptosis in neonatal rats, decrease the ratio of p-CRMP2/CRMP2 and increase the expression of CRMP2 may be one of the mechanisms for neuroprotection and this Conclusion may provide the theoretic foundation for reasonable selection of anaesthetics.