Role of p-ERK1/2 in 17β estradiol-induced inhibition of propofol-caused neuroapoptosis in hippocampus of newborn rats

Objective To evaluate the role of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in 17β estradiol-induced inhibition of propofol-caused neuroapoptosis in the hippocampus of newborn rats. Methods Seventy-eight male Sprague-Dawley rats, aged 7 days, weighing 11-18 g, were divided into 6 groups (n=13 each) using a random number table: dimethyl sulfoxide (DMSO) group, fat emulsion group (group F), 17β estradiol group (group E), propofol group (group P), propofol plus 17β estradiol group (group PE) and propofol plus17β estradiol plus mitogen-activated protein kinase kinase 1/2 inhibitor U0126 group (group PEU).17β estradiol 600 μg/kg was injected subcutaneously every 24 h for 7 consecutive days in group E, and the equal volume of DMSO was given instead in group DMSO.Propofol 75 mg/kg was injected intraperitoneally every 24 h for 7 consecutive days in group P, and the equal volume of fat emulsion was injected instead in group F. Propofol 75 mg/kg was injected intraperitoneally, and 17β estradiol 600 μg/kg was injected subcutaneously every 24 h for 7 consecutive days in group PE.Propofol 75 mg/kg was injected intraperitoneally, 17β estradiol 600 μg/kg was injected subcutaneously, and U0126 10 mg/kg was injected intraperitoneally every 24 h for 7 consecutive days in group PEU.At 15 min after the last injection, 3 rats in each group were randomly selected, and arterial blood samples from the cardiac apex were collected for determination of arterial oxygen partial pressure.The animals were sacrificed at 24 h after the last injection for determination of the expression of activated caspase-3 (by immunohistochemistry) and p-ERK1/2 (by Western blot). Results There was no significant difference in arterial oxygen partial pressure between the six groups (P>0.05). Compared with group F, the expression of activated caspase-3 was significantly up-regulated, and the expression of p-ERK1/2 was down-regulated in group P (P<0.05). Compared with group P, the expression of activated caspase-3 was significantly down-regulated, and the expression of p-ERK1/2 was up-regulated in group PE (P<0.05). Compared with group PE, the expression of activated caspase-3 was significantly up-regulated, and the expression of p-ERK1/2 was down-regulated in group PEU (P<0.05). Conclusion The mechanism by which 17β estradiol inhibits propofol-caused neuroapoptosis in the hippocampus is related to up-regulation of the expression of p-ERK1/2 in newborn rats. Key words: Extracellular signal-regulated kinase(ERK); Propofol; 17βestradiol; Apoptosis; Hippocampus