慢性锰染毒对大鼠学习记忆能力及其血浆脑源性神经营养因子含量的影响

[目的]观察不同剂量慢性锰染毒对大鼠学习记忆能力及其对血浆脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）含量的影响,探讨血浆BDNF含量作为锰致大鼠学习记忆功能损害效应生物标志的可行性。[方法]将40只雄性SD大鼠随机分为对照组及低（5 mg/kg）、中（10 mg/kg）、高（20 mg/kg）剂量染猛组,腹腔注射染毒,每周5 d,连续18周。分别于染毒第6、12、18周,通过Morris水迷宫实验检测大鼠的学习记忆能力。于第18周末次染毒24 h后,采血并分离血浆,用石墨炉原子吸收光谱法和ELISA试剂盒分别检测大鼠血浆锰及BDNF含量。[结果]在第6周的水迷宫实验中,与对照组相比,高剂量组逃避潜伏期延长,穿越平台次数下降（均为P〈0.05）;在第12、18周测试中,与对照组相比,中、高剂量组逃避潜伏期延长,而各染锰组的穿越平台次数均下降（均为P〈0.05）。与对照组血浆锰含量[（13.16±5.45）μg/L]相比,低、中、高剂量染锰组的血浆锰含量均升高[分别为（55.84±11.62）、（82.21±8.26）、（115.58±21.31）μg/L,均为P〈0.05）;与对照组血浆BDNF含量[（232.64±75.37）ng/L]相比,中、高剂量染锰组的血浆BDNF含量均下降[分别为（145.80±46.14）、（93.21±44.92）ng/L,均为P〈0.05]。血浆BDNF含量与穿越平台次数呈正相关,与逃避潜伏期及血浆锰含量呈负相关（均为P〈0.05）。[结论]慢性锰染毒可致大鼠空间学习记忆能力下降,并降低血浆BDNF含量,血浆BDNF似可考虑作为锰染毒致大鼠学习记忆功能损害的效应生物标志。

Effects of Chronic Manganese Exposure on Learning and Memory and Expression of Plasma Brain-Derived Neurotrophic Factor in Rats

[Objective] To examine the effects of chronic manganese exposure on learning and memory and expression of brain-derived neurotrophic factor（BDNF） in rat, and explore whether plasma BDNF can be used as an effect biomarker of manganese exposure. [Methods] Male Sprague-Dawley rats（n=40） were equally divided into 4 groups： control, low-, middle-, and highdose groups which received 0, 5, 10, and 20 mg/kg of manganese by intraperitoneal injection for 18 weeks, 5 d/week, respectively. Learning and memory was evaluated by Morris water maze task during six consecutive days at the 6th, 12 th, and 18 th weeks. The levels of plasma manganese and BDNF were detected by graphite furnace atomic absorption spectrometry（GFAAS） and ELISA kit, respectively. [Results] Compared to the control, increases in escape latency and decreases in platform crossings of the high-dose group were noted at the 6th week（P 〈0.05）. Similarly, compared to the control, increases in escape latency and decreases in platform crossings of the middle- and high-dose groups were noted at the 12 th and 18 th weeks（both P 〈0.05）. Compared to the control group [（13.16±5.45） μg/L], the plasma manganese levels were higher in the low-, middle-, and high-dose groups [（55.84±11.62）,（82.21±8.26）, and（115.58±21.31） μg/L, respectively]（all P 〈0.05）. Compared to the control group [（232.64±75.37） ng/L], the plasma BDNF levels were lower in the middle- and high-dose groups [（145.80±46.14） and（93.21±44.92） ng/L, respectively]（both P 0.05）. The plasma BDNF levels were positively correlated with the number of platform crossings, and negatively correlated with the escape latency and the plasma manganese levels（both P 〈0.05）. [Conclusion] The rats treated with chronic manganese exposure may suffer deficits in spatial learning and memory and the down-regulated expression of plasma BDNF, suggesting that plasma BDNF might be an effect biomarker of manganese exposure.