Résumé
Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.Methods:Eighty 7-day-old clean-grade healthy newborn Sprague-Dawley rats of both sexes, weighing 11-17 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), 17β estradiol plus propofol group (EP group) and 17β estradiol plus propofol plus BDNF/TrkB signaling pathway blocker K252a group (K group). Propofol 80 mg/kg was intraperitoneally injected every day for 5 days in P, EP and K groups.The equal volume of fat emulsion was given instead in group C. In EP and K groups, 17β estradiol 600 μg/kg was subcutaneously injected at 30 min before propofol injection.BDNF/TrkB signaling pathway blocker K252a 100 μg/kg was intraperitoneally injected in group K. Morris water maze test was performed on days 30-34 after birth to assess the cognitive function.The rats were sacrificed after the end of Morris water maze test, and the hippocampal tissues were removed for determination of the apoptosis rate of hippocampal neurons (by flow cytometry), expression of BDNF, p-Trkb and cleaved caspase-3 (by Western blot and immunofluorescence), and expression of Bcl-2 and Bax mRNA (by real-time polymerase chain reaction) and for microscopic examination of the pathological changes in hippocampal CA1 region (with a light microscope). Bax mRNA/Bcl-2 mRNA ratio was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased ( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group P. Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of BDNF and p-TrkB was up-regulated, the expression of cleaved caspase-3 was down-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were decreased( P<0.05), and the pathological changes in hippocampal CA1 region were attenuated in group EP.Compared with group EP, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of BDNF and p-TrkB was down-regulated, the expression of cleaved caspase-3 was up-regulated, the apoptosis rate of hippocampal neurons and Bax mRNA/Bcl-2 mRNA ratio were increased( P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group K. Conclusions:BDNF/TrkB signaling pathway is involved in 17β estradiol-induced reduction of long-term cognitive impairment induced by multiple propofol anesthesia in developing rats.