Role of TRPM2 in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of transient receptor potential melastatin2 (TRPM2) in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.Methods:Sixty SPF-grade healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group M) and sevoflurane anesthesia+ TRPM2 inhibitor group (group M+ A). M and M+ A groups inhaled 2% sevoflurane for 5 h. In group M+ A, TRPM2 inhibitor ACA 20 mg/kg was intraperitoneally injected at 1 h before sevoflurane inhalation, and the equal volume of dimethyl sulfoxide was intraperitoneally injected in group C and group M. Morris water maze test was performed at 1 day after sevoflurane anesthesia. The escape latency, times of crossing the original platform and time spent in the original platform quadrant were collected. The expression of TRPM2 and necroptosis-related proteins (mixed lineage kinase domain-like protein [MLKL], receptor-interacting protein kinase-1 [RIPK1], phosphorylated MLKL [p-MLKL], and phosphorylated RIPK1 [p-RIPK1]) was detected by Western blot. The cytosolic Ca 2+ concentration in and necroptosis rate of hippocampal neurons were determined by flow cytometry. Results:Compared with group C, the escape latency was significantly prolonged, the times of crossing the original platform were decreased and the time spent in the original platform quadrant was shortened, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was up-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were increased in group M and group M+ A ( P<0.05). Compared with group M, the escape latency was significantly shortened, the times of crossing the original platform were increased, and the time spent in the original platform quadrant was prolonged, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was down-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were decreased in group M+ A ( P<0.05). Conclusions:Hippocampal TRPM2 is involved in the process of sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.