Effect and mechanism of dexmedetomidine on propofol-induced apoptosis of cortical neurons in rats

Abstract

Objective To investigate the mechanisms of the protective effects of dexmedetomidine against the propofol-induced neuroapoptosis in primary cultured cortical neurons. Methods The neurons were cultured 7days and then divided into four groups: vehicle-control group (treated with equal volume of intralipid), propofol-treated group (treated with 500 μmol/L propofol), propofol plus dexmedetomidine treated group( treated with 500 μmol/L propofol and 0.1 μmol/L dexmedetomidine), and LY294002 pretreated group( treated with 500 μmol/L propofol , 0.1 μmol/L dexmedetomidine and 10 μmol/L LY294002 ). 12 hours after different treatments, neuron viability was measured by MTT assay, neuroapoptosis was detected by Hoechst33258 staining, and the levels of pAkt and Bcl-2 protein were detected by Western blot. Results Compared with the vehicle-reduced group, propofol reduced neuron viability greatly((53.4±4.2)% vs(99.9±6.3)% ; P<0.01), but increased neuroapoptosis greatly((44.6±4.3)% vs(5.8±0.4)% ; P<0.01). The levels of pAkt((0.41±0.03)vs(0.86±0.07))and Bcl-2 ((0.15±0.02)vs (0.72±0.03)) were decreased greatly (both P<0.01). Compared with propofol treatment group, the neuron viability of propofol plus dexmedetomidine group were increased greatly((86.4±5.3)% , P<0.01), the neuroapoptosis was decreased greatly((23.1±3.5)%, P<0.01), and the levels of pAkt(0.8±0.03)and Bcl-2 (0.52±0.05)were increased greatly (both P<0.01). Compared with propofol plus dexmedetomidine treated group, LY294002 inhibited the protective effects of dexmedetomidine, decreased neuron viability greatly((64.3±5.1)% , P<0.01), increased the number of apoptotic neurons((38.8±4.9)%, P<0.01), and reduced the levels of pAkt(0.52±0.04)and Bcl-2(0.31±0.02) significantly (P<0.01). Conclusion Dexmedetomidine exerts the neuroprotective effects against propofol-induced neuroapoptosis by activating the PI3K-Akt-Bcl-2 signalling pathway. Key words: Propofol; Dexmedetomidine; Primary cultured cortical neurons; Apoptosis; PI3K-Akt -Bcl-2 signalling pathway