Relationship between dexmedetomidine-induced reduction of sevoflurane-induced neurotoxicity and NKCC1/KCC2 in neonatal rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between dexmedetomidine-induced reduction of sevoflurane-induced neurotoxicity and cation-chloride cotransporters Na + -K + -2Cl --1 (NKCC1) /K + -2Cl --2 (KCC2) in neonatal rats. Methods:Eighty healthy male Sprague-Dawley rats at postnatal day 7 were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), dexmedetomidine group (group D), and sevoflurane and dexmedetomidine group (group SD). Rats were exposed to 2.5% sevoflurane for 6 h to establish the model of sevoflurane anesthesia in group S. Dexmedetomidine 1.0 μg/kg was intraperitoneally injected, and then sevoflurane anesthesia was performed in group SD.The expression of cleaved caspase-3, NKCC1 and KCC2 was detected by Western blot at 24 h after the end of anesthesia.At 35 days after the end of anesthesia, the cognitive function was assessed using the Y maze test, and the neurons in the hippocampal CA1 area were counted using the Nissan staining method. Results:Compared with group C, the percentage of time spent in novel arm and the number of neurons in hippocampal CA1 area were significantly decreased, the expression of cleaved caspase-3 and NKCC1 was up-regulated, the expression of KCC2 was down-regulated, and the ratio of NKCC1/KCC2 was increased in S and SD groups ( P<0.05), and no change was found in the above indicators in group D ( P>0.05). Compared with group S, the percentage of time spent in novel arm and the number of neurons in hippocampal CA1 area were significantly increased, the expression of cleaved caspase-3 and NKCC1 was down-regulated, the expression of KCC2 was up-regulated, and the ratio of NKCC1/KCC2 was decreased in group SD ( P<0.05). Conclusion:The mechanism of dexmedetomidine attenuating sevoflurane-induced neurotoxicity may be related to maintaining the relatively stable expression of NKCC1/KCC2 in neonatal rats.