Neuroprotection Of Progesterone On Neonatal Rats After Sevoflurane Inhalation Anesthesia

Objective:To investigate neuroprotection of progesterone on neonatal rats after sevoflurane inhalation anesthesia and whether progesterone receptors play a key role in it.Methods:A total of 160 newborn Sprague-Dawley rats were randomly divided into four groups(n=40): blank control group(C group),sevoflurane group(S group),progesterone + sevoflurane group(S+P group)and progesterone + sevoflurane + ulipristal acetate group(S+P+U group),half male and female in each group.The rats in S group were exposed to 3% sevoflurane for two hours on postnatal days(P)seventh,eighth and ninth,which was used to establish developmental sevoflurane neurotoxicity model.The rats in drug intervention groups received a daily subcutaneous injection of progesterone(8 mg/kg)or progesterone plus ulipristal acetate(3 mg/kg)at P4 to P9,and then were exposed to 3% sevoflurane for 3 consecutive days at P7 to P9.The apoptosis of nerve cells in CA1 area of hippocampus was evaluated by TUNEL assays in neonatal rats.The relative experssion of apoptosis protein(caspase-3)in hippocampus was also determined by western blot.Rats in each group were evaluated for the space orientation ability and the learning and memory ability by Y maze,Morris water maze test and platform test 6 weeks after birth.Results:1.Compared with C group,sevoflurane significantly increased the neuronal apoptosis in CA1 area of the hippocampus in the central nervous system of newborn rats and increased the expression of caspase-3 in hippocampus(P<0.01)and caused irreversible damage to hippocampal nerve cells in the later stage of development.Compared with S group,progesterone can significantly reduced neuronal apoptosis induced by sevoflurane and reduced the expressions of caspase-3 in hippocampus(P<0.01)and can partially reverse the morphological changes of late-developing nerve cells.Compared with S+P group,the neuronal apoptosis in CA1 area of the hippocampus and the expression of caspase-3 in hippocampus were both increased in S+P+U group(P<0.05)and the nerve cells in the late stage of development also deteriorated.2.The results of the Y maze experiment showed that sevoflurane reduced the alternation score of rats(P<0.05);pretreatment with progesterone could increase the alternation score of rats after sevoflurane anesthesia(P<0.05);application of progesterone receptor blockers can antagonize the effects of progesterone and reduce the alternating score rate of rats(P<0.05).The results of the water maze experiment showed that sevoflurane prolonged the time required for rats to find a platform in the water maze(P<0.05),and reduced the residence time of the rats in the target quadrant(P<0.05);pretreatment with progesterone could shorten the time required for rats to find a platform in the water maze after sevoflurane anesthesia(P<0.05)and increase the residence time in the target quadrant(P<0.05);progesterone receptor blockers can antagonize the effects of progesterone,the time required for rats to find a platform in the water maze was extended(P<0.05),and the residence time in the target quadrant was reduced(P<0.05).The results of the platform jumping experiments showed that sevoflurane significantly shortened the platform latency of rats(P<0.01)and increased the number of errors in platform diving(P<0.01).The application of progesterone pretreatment could significantly extend the platform latency of rats(P<0.05),reducing the number of errors in platform jumping(P<0.01);application of progesterone receptor blockers can antagonize the effect of progesterone,shorten the latency period of platform jumping(P<0.05),and increase the number of errors(P<0.05).Conclusion:1.Repeated inhalation of 3% sevoflurane in neonatal rats can cause neurotoxic damage and induce cognitive dysfunction.2.Progesterone may have a neuroprotective effect on the neurotoxic damage of neonatal rats induced by sevoflurane,in which progesterone receptors may play some roles.