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目的:评价脑源性神经营养因子(BDNF)/酪氨酸激酶受体B(TrkB)信号通路在17β雌二醇减轻多次丙泊酚麻醉致发育期大鼠远期认知功能障碍中的作用。方法:清洁级健康新生SD大鼠80只，7日龄，体重11~17 g，雌雄不拘，采用随机数字表法分为4组(n n＝20)：对照组(C组)、丙泊酚组(P组)、17β雌二醇+丙泊酚组(EP组)和17β雌二醇+丙泊酚+BDNF/TrkB信号通路阻断剂组(K组)。P组、EP组和K组每天腹腔注射丙泊酚80 mg/kg，共注射5 d，C组腹腔注射等量脂肪乳剂。EP组和K组大鼠丙泊酚注射前30 min皮下注射17β雌二醇600 μg/kg，K组大鼠腹腔注射BDNF/TrkB信号通路阻断剂K252a 100 μg/kg。于出生后30~34 d时行Morris水迷宫实验检测大鼠认知功能，随后处死大鼠分离海马组织，采用流式细胞术确定海马细胞凋亡率，Western blot法和免疫荧光技术检测BDNF、p-TrkB和裂解的caspase-3(cleaved caspase-3)表达，采用RT-PCR法检测Bcl-2和Bax的mRNA表达，计算Bax mRNA/Bcl-2 mRNA比值，光镜下观察海马CA1区病理学结果。n 结果:与C组比较，P组大鼠逃避潜伏期延长，穿越原平台位置次数减少，BDNF和p-TrkB表达下调，cleaved caspase-3表达上调，海马细胞凋亡率和Bax mRNA/Bcl-2 mRNA比值增加(n P<0.05)，海马CA1区病理学损伤加重。与P组比较，EP组大鼠逃避潜伏期缩短，穿越原平台位置次数增加，BDNF和p-TrkB表达上调，cleaved caspase-3表达下调，海马细胞凋亡率和Bax mRNA/Bcl-2 mRNA比值降低(n P<0.05)，海马CA1区病理学损伤减轻。与EP组比较，K组大鼠逃避潜伏期延长，穿越原平台位置次数减少，BDNF和p-TrkB表达下调，cleaved caspase-3表达上调，海马细胞凋亡率和Bax mRNA/Bcl-2 mRNA比值增加(n P<0.05)，海马CA1区病理学损伤加重。n 结论:BDNF/TrkB信号通路参与了17β雌二醇减轻多次丙泊酚麻醉致发育期大鼠远期认知功能障碍的过程。“,”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 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.n 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 (n 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(n 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(n P<0.05), and the pathological changes in hippocampal CA1 region were accentuated in group K.n 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.