Mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity in neonatal rats: relationship with Ngb / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity and the relationship with neuroglobin (Ngb) in neonatal rats.Methods:Eighty-four healthy male Sprague-Dawley rats, aged 7 days, weighing 12-16 g, were divided into 4 groups ( n=21 each) using a random number table method: control group (group C), sevoflurane group (group S), sevoflurane plus dexmedetomidine group (group SD), and sevoflurane plus dexmedetomidine and yohimbine group (group SDY). Sevoflurane anesthesia method: anesthesia was induced by inhaling 8% sevoflurane and then maintained by inhaling 3% sevoflurane for 4 h. At the end of anesthesia, dexmedetomidine 50 μg/kg was intraperitoneally injected in group SD, and 0.5 mg/kg yohimbine (α 2 adrenergic receptor antagonist) was intraperitoneally injected immediately after the end of intraperitoneal injection of dexmedetomidine 50 μg/kg in group SDY.Six rats were randomly selected from each group and sacrificed at 24 h after the end of anesthesia.The brain tissues were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), the expression of Ngb in the area of the hippocampus (by immunofluorescence staining) and the expression of cytochrome C (Cyt c) and caspase-3 (by Western blot). The other rats were fed until 28 days old, and Morris water maze test was performed. Results:Compared with group C, the expression of Ngb, Cyt c and caspase-3 was significantly up-regulated ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was increased in group S. Compared with group S, the expression of Ngb was significantly up-regulated, expression of Cyt c and caspase-3 was down-regulated, the escape latency was shortened ( P<0.05), histopathologic changes in hippocampal CA1 region were reduced, and Ngb fluorescence intensity was increased in group SD.Compared with group SD, the expression of Ngb was significantly down-regulated, expression of Cyt c and caspase-3 was up-regulated, the escape latency was prolonged ( P<0.05), histopathologic changes in hippocampal CA1 region were accentuated, and Ngb fluorescence intensity was decreased in group SDY. Conclusion:The mechanism by which dexmedetomidine reduces sevoflurane-induced neurotoxicity may be related to activating α 2 adrenergic receptors and up-regulating the expression of Ngb in neonatal rats.