左旋肉碱对氯化汞致大鼠神经毒性的拮抗作用

Protection effect of L-carnitine against the neurotoxicity induced by HgCl_2 in the rats

目的探索抗氧化剂左旋肉碱(L-Car)对环境污染物氯化汞(HgCl2)致大鼠神经毒性作用的拮抗作用。方法将48只SPF级40 d龄♂SD大鼠随机均分为6组,HgCl2和/或L-Car连续饮水暴露4周,分别在暴露前、后的第7、14、21、28天对大鼠称重,并进行旷场实验和被动游泳实验;暴露后将大鼠断头处死,迅速分离整脑并称重,测定大脑皮层匀浆液中活性氧(ROS)、丙二醛(MDA)和超氧化物歧化酶(SOD)的表达情况。结果大鼠饮水暴露后,0.06 g·L-1HgCl2组大鼠的体重从第7天开始受到明显抑制,大脑/体重比也显著高于对照组(P<0.01)。旷场实验和被动游泳实验表明:0.06 g·L-1HgCl2组大鼠的行为学改变最明显,第7天大鼠的自主活动明显减弱(P<0.05),随后开始恢复,第14天表现出自主活动亢进,到第28天自主活动度再次表现为显著抑制。大鼠大脑皮层中ROS和MDA的量在各剂量组均增加(P<0.05);SOD的活性则表现为降低的趋势,只有0.06 g·L-1HgCl2组显著降低(P<0.05)。L-Car处理后可显著改善HgCl2所致的上述变化。结论汞具有神经毒性作用,L-Car对HgCl2的神经毒性具有拮抗作用。

OBJECTIVE To evaluate whether L - carnitine （ L - Car） has protection effect against neurotoxicity induced by HgCl2 or not. METHODS Young adult male SD rats （ 180 - 200 g, about 40 days old） were divided into six groups randomly （ n = 8 ） and administered with HgCl2 and/or L - Car via drinking water for 4 weeks. The rats body weight were recorded each week, Open - field test （OFT） and forced -swimming test （FST） were performed on days 0, 7, 14, 21, 28. All rats were decapitated, the brains were rapidly removed and weighed. Reactive oxygen species （ROS） , malondialdehyde （MDA） and superoxide dismutase （ SOD ） were measured by Assay Kits in rats＇ cerebral cortex at terminal time - point. RESULTS The body weight decreased significantly during HgCl2 administration from days 7, the ratio brain weight/body weight was significate higher than control group. The spontaneous locomotor activities of rats decreased at first （ 7 d,P 〈 0.05 ） and then excitability and aggressiveness increased （ 14 d, P 〈 0.05 ）. After 4 weeks treatment the activities decreased significantly again in HgC12 0.06 g. L^-1 group. ROS and MDA were increased significantly in all HgCl2 groups （ P 〈 0.05 ）, SOD was decreased only in HgCl 2 0.06 g·L^-1 group （ P 〈 0.05 ）. However, those effects on behavior and biochemical assays were attenuated if 1.5 g.L^-1 L - Car simultaneous administrated. CONCLUSION The results suggested L - Car was a potential pharmacological agent with protection against the neurotoxicity of HgCl2.