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目的:探讨雷帕霉素靶蛋白（mTOR）在镧致子代大鼠大脑皮质神经细胞损伤中的作用及对仔鼠大脑发育和学习记忆的影响。方法:选择成年雌、雄性Wistar大鼠各32只，按体重采用随机数字表法分为4组，每组16只，雌雄各半。雌鼠分别饮用不同含量的氯化镧溶液[0.0（对照）、2.5、5.0、10.0 g/L]，而雄鼠正常饮水。将雌鼠和雄鼠按照1∶1方式入笼进行交配，雌性大鼠自妊娠期开始染镧，其仔鼠染镧至断乳后4周。对4组仔鼠进行Morris水迷宫实验，通过空间探索观察镧对仔鼠学习记忆的影响；取仔鼠大脑皮层，尼氏染色后镜下观察皮质尼氏体数量变化。采用实时荧光定量PCR法测定仔鼠大脑皮层神经细胞mTOR mRNA表达水平；采用蛋白免疫印迹（Western blot）法检测仔鼠皮质神经细胞磷酸化mTOR（p-mTOR）蛋白含量。结果:与对照组[（121.75 ± 11.20）g、（1.43 ± 0.10）%、（0.86 ± 0.08）%]比较，2.5、5.0、10.0 g/L染镧组仔鼠体重明显下降[（110.00 ± 11.59）、（98.88 ± 7.95）、（85.63 ± 7.25）g，n P均< 0.05]；脑组织系数、皮质系数明显升高[（1.56 ± 0.18）%、（1.66 ± 0.14）%、（1.89 ± 0.16）%，（0.94 ± 0.08）%、（1.01 ± 0.07）%、（1.08 ± 0.09）%，n P均< 0.05]。5.0、10.0 g/L染镧组脑重[（1.63 ± 0.05）、（1.61 ± 0.03）g]明显低于对照组和2.5 g/L染镧组[（1.73 ± 0.06）、（1.70 ± 0.06）g，n P均< 0.05]。与对照组（53.25 ± 9.93）比较，各染镧组仔鼠大脑皮质神经细胞尼氏体数量（36.13 ± 3.98、27.50 ± 5.21、13.63 ± 5.93）明显下降（n P均< 0.05）。空间探索实验结果显示，与对照组[（5.75 ± 1.98）次、（10.69 ± 2.96）s、（3.75 ± 1.28）次]比较，10.0 g/L染镧组仔鼠穿过目标象限次数[（3.63 ± 1.41）次]、在目标象限停留时间[（5.12 ± 2.09）s]明显降低（n P均< 0.05），5.0、10.0 g/L染镧组仔鼠穿过平台次数[（1.88 ± 0.84）、（1.13 ± 1.12）次]明显降低（n P均< 0.05）。皮质组织mTOR mRNA（1.00 ± 0.28、0.74 ± 0.19、0.58 ± 0.13、0.45 ± 0.29）和p-mTOR蛋白表达水平（0.69 ± 0.07、0.33 ± 0.06、0.30 ± 0.04、0.17 ± 0.03）组间比较差异有统计学意义（n F = 8.33、139.12，n P均< 0.05）。n 结论:镧暴露可损伤皮质神经细胞，影响仔鼠大脑发育。镧通过降低仔鼠大脑mTOR mRNA和p-mTOR蛋白表达水平以及空间探索观察能力，致仔鼠学习记忆能力下降。“,”Objective:To investigate the role of rapamycin target protein (mTOR) in lanthanum-induced injury of cerebral cortical neurons in offspring rats, and the effect on brain development, learning and memory ability of offspring rats.Methods:Thirty-two adult female and 32 male Wistar rats, were randomly divided into 4 groups according to their body weight, with 16 rats in each group (half female and half male). Female rats were fed with different amounts of lanthanum chloride[0.0 (control), 2.5, 5.0, 10.0 g/L], while male rats drank normal water. Female and male rats were mated in cages at a ratio of 1∶1. Female rats began to be exposed to lanthanum from pregnancy, while their offspring were exposed to lanthanum until 4 weeks after weaning. Morris water maze experiment was carried out in the 4 groups of offspring rats, and the effects of lanthanum on learning and memory were observed by space exploration. The cerebral cortex of offspring rats was taken, and the amount of Nissl body was observed under microscope after Nissl staining. The expression of mTOR mRNA in offspring rats cerebral cortex nerve cells was measured by real-time quantitative PCR. Western blotting was used to detect the protein content of p-mTOR in offspring rats cortical neurons.Results:Compared with the control group, the body weight of offspring rats exposed to lanthanum at 2.5, 5.0 and 10.0 g/L was significantly decreased [(121.75 ± 11.20), (110.00 ± 11.59), (98.88 ± 7.95) and (85.63 ± 7.25) g, n P < 0.05], and the brain tissue coefficient and cortical coefficient were significantly increased [(1.43 ± 0.10)%, (1.56 ± 0.18)%, (1.66 ± 0.14)%, (1.89 ± 0.16)%; (0.86 ± 0.08)%, (0.94 ± 0.08)%, (1.01 ± 0.07)%, (1.08 ± 0.09)%, n P < 0.05]. The brain weight [(1.63 ± 0.05), (1.61 ± 0.03) g] of 5.0 and 10.0 g/L lanthanum-exposed groups were significantly lower than those in the control group and 2.5 g/L lanthanum-exposed group [(1.73 ± 0.06), (1.70 ± 0.06) g, n P < 0.05]. Compared with the control group (53.25 ± 9.93), the amounts of Nissl body in cerebral cortical neurons in different lanthanum-exposed groups (36.13 ± 3.98, 27.50 ± 5.21, 13.63 ± 5.93) were significantly decreased ( n P < 0.05). The results of space exploration experiment showed that compared with the control group [(5.75 ± 1.98) times, (10.69 ± 2.96) s, (3.75 ± 1.28) times], the times of entering the target quadrant [(3.63 ± 1.41) times] and the stay time in the target quadrant [(5.12 ± 2.09) s] in 10.0 g/L lanthanum-exposed group were significantly reduced ( n P < 0.05), and the times of entering the platform [(1.88 ± 0.84), (1.13 ± 1.12) times] in 5.0 and 10.0 g/L lanthanum-exposed groups were significantly reduced ( n P < 0.05). There were significant differences in mTOR mRNA (1.00 ± 0.28, 0.74 ± 0.19, 0.58 ± 0.13, 0.45 ± 0.29) and p-mTOR protein expression levels (0.69 ± 0.07, 0.33 ± 0.06, 0.30 ± 0.04, 0.17 ± 0.03) in cortical tissues ( n F = 8.33, 139.12, n P < 0.05).n Conclusion:Lanthanum exposure can damage cortical neurons, affect the brain development of offspring rats, reduce the expression of mTOR mRNA and p-mTOR protein in the brain of offspring rats, reduce the ability of space exploration and observation, resulting in the decline of learning and memory ability of offspring rats.