Neuroprotection of progesterone on neonatal rats after sevoflurane inhalation anesthesia / 解放军医学杂志

ABSTRACT

[Abstract] Objective To investigate the neuroprotection of progesterone on neonatal rats after sevoflurane inhalation anesthesia and its mechanisms. Methods A total of 120 newborn Sprague-Dawley rats were randomly divided into three groups (n=40) blank control group (group C), sevoflurane group (group S) and progesterone plus sevoflurane group (group S+P), half male and half female in each group. The rats in group S were exposed to 3% sevoflurane for two hours on postnatal days (P) seven, eight and nine, which was used to establish the developmental sevoflurane neurotoxicity model. The rats in group C were exposed to mixture of gases (2 L/min, 2 hours a day). The rats in group S+P received a daily injection of progesterone (8 mg/kg) from P4 to P9 and then were exposed to 3% sevoflurane (2 L/min, 2 hours a day) for 3 consecutive days between P7 to P9. The apoptosis of nerve cells in the CA1 area of the hippocampus evaluated by TUNEL assays in neonatal rats. The relative expression of apoptosis protein (caspase-3) in the hippocampus determined by Western blotting. Rats in each group evaluated for the space orientation ability and the learning and memory ability by Y maze, Morris water maze and platform test 6 weeks after birth. Results 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 the hippocampus (P<0.01); progesterone significantly reduces neuronal apoptosis which induced by sevoflurane and the expression of Caspase-3 in the hippocampus (P<0.01). The results of the Y maze, Morris water maze and platform test showed that sevoflurane reduced the alternating scoring rate of rats (P<0.05), prolonged the time required to find the platform in the water maze (P<0.05) and increased the number of errors in the platform test (P<0.01). Progesterone significantly increased the alternating scoring rate of rats (P<0.05), shortened the time required to find the platform in the water maze (P<0.05) and significantly reduced the number of errors in the platform test (P<0.01). Conclusion Repeated inhalation of 3% sevoflurane in neonatal rats can cause neurotoxic damage and induce cognitive dysfunction. Progesterone may have a neuroprotective effect on the neurotoxic damage of neonatal rats induced by sevoflurane.