Role of GPR30 in 17β estradiol-induced inhibition of ketamine-caused neuroapoptosis in hippocampus of newborn rats: the relationship with p-ERK1/2 / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of G protein-coupled receptor 30 (GPR30) in 17β estradiol-induced inhibition of ketamine-caused neuroapoptosis in the hippocampus of newborn rats and the relationship with phosphorylated extracellular signal-regulated kinase 1/2 (p-ERKl/2).Methods Twentyfour clean-grade healthy male Sprague-Dawley rats,aged 7 days,weighing 11-18 g,were divided into 4 groups (n =6 each) using a random number table method:control group (group C),ketamine group (group K),17β estradiol plus ketamine group (group EK),and GPR30 inhibitor G15 plus 17β estradiol plus ketamine group (group G15EK).Ketamine 75 mg/kg (diluted to 0.1 ml in normal saline) was intraperitoneally injected every 24 h for 3 consecutive days in group K.In group EK,17β estradiol 600 μg/kg was subcutaneously injected and ketamine 75 mg/kg was intraperitoneally injected every 24 h for 3 consecutive days.G15 300 μg/kg and 17β estradiol 600 μg/kg were subcutaneously injected and ketamine 75 mg/kgwas intraperitoneally injected every 24 h for 3 consecutive days in group G15EK.The equal volume of normal saline 0.1 ml was intraperitoneally injected instead in group C.The animals were sacrificed at 24 h after the last injection for determination of the expression of cleaved caspase-3,ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) (by Western blot).Results There was no significant difference in the expression of ERK1/2 in hippocampus among the four groups (P＞0.05).Compared with group C,the expression of cleaved caspase-3 was significantly up-regulated,and the expression of p-ERK1/2 was down-regulated in K and G15EK groups (P＜0.05).Compared with group K,the expression of cleaved caspase-3 was significantly down-regulated,and the expression of p-ERK1/2 was up-regulated in group EK (P＜0.05).Compared with group EK,the expression of cleaved caspase-3 was significantly up-regulated,and the expression of p-ERK 1/2 was down-regulated in group G15EK (P＜0.05).Conclusion GPR30 is involved in 17β estradiol-induced inhibition of ketamine-caused neuroapoptosis in the hippocampus of newborn rats,which is related to up-regulating the expression of p-ERKl/2.