Effect of ulinastatin on isoflurane-induced neuronal apoptosis in the hippocampus of rats / 南方医科大学学报

ABSTRACT

OBJECTIVE@#To investigate the effect of ulinastatin pretreatment on isoflurane-induced mitochondria-dependent neuronal apoptosis in the hippocampus of rats.@*METHODS@#Thirty-six male SD rats were randomly assigned into control group, isoflurane group and ulinastatin group. In the latter two groups, the rats were subjected to acute exposure to 0.75% isoflurane for 6 h and pretreated with 50 000 U/kg of ulinastatin before isoflurane exposure, respectively. After the treatments, apoptosis of the hippocampal neurons was detected using TUNEL assay, and the mitochondrial membrane potential (△ ψm) was measured using JC-1 mitochondrial membrane potential kit; cytochrome C release and caspase-3 activity were examined with Western blotting, and intracellular reactive oxygen species (ROS) was detected using the fluorescent probe H2DCFDA.@*RESULTS@#Compared with those in the control group, the rats with acute exposure to isoflurane showed markedly increased TUNEL-positive cells in the hippocampus ( < 0.05), which were obviously reduced by ulinastatin pretreatment ( < 0.05). The △ψm of the hippocampal neurons was significantly reduced after isoflurane exposure ( < 0.05), and was partly recovered by ulinastatin pretreatment ( < 0.05). Acute exposure to isoflurane resulted in obviously increased cellular ROS, cytochrome C release and caspase-3 activity in the hippocampal neurons ( < 0.05), and these changes were significantly inhibited by ulinastatin pretreatment ( < 0.05).@*CONCLUSIONS@#Ulinastatin pretreatment provides neuroprotection against isoflurane-induced apoptosis of the hippocampal neurons in rats possibly by inhibiting mitochondria-dependent apoptosis pathway.