牛磺酸对甲醛及苯系物混合暴露所致幼年大鼠学习记忆功能损伤的保护作用
Protective effects of taurine on learning and memory impairment after exposure to formaldehyde and benzene analogues in young rats
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摘要:
背景 甲醛及苯系物作为常见的环境污染物，其神经毒性引起了人们的广泛关注。
目的 探讨牛磺酸对甲醛及苯系物混合暴露所致幼年大鼠认知功能损伤的改善作用。
方法 将24只4周龄的SD大鼠随机分为4组，每组6只，分别为对照组（洁净空气）、模型组（5 mg·m−3甲醛+5 mg·m−3苯+10 mg·m−3甲苯+10 mg·m−3二甲苯）、低剂量牛磺酸干预组（5 g·L−1牛磺酸+甲醛及苯系物混合物）和高剂量牛磺酸干预组（10 g·L−1牛磺酸+甲醛及苯系物混合物），经气溶胶口鼻式吸入暴露28 d。暴露染毒结束后，通过Morris水迷宫实验测定动物的学习记忆功能。行为测试结束后，将大鼠麻醉处死，取脑组织用于组织病理学及分子生物学检测。采用Tunel检测海马CA1区神经细胞凋亡率，采用Western blotting检测海马组织中凋亡相关蛋白半胱天冬酶3（caspase 3）、bax、bcl-2的表达量。
结果 吸入染毒期间各组大鼠的生长发育均未受到显著影响。Morris水迷宫实验期间，在训练的第3天—第5天均发现牛磺酸干预组大鼠的逃避潜伏期与对照组无差异（
P >0.05），而模型组大鼠的逃避潜伏期明显高于对照组（P <0.05）；高剂量牛磺酸干预组大鼠穿越平台次数、目标象限停留时间均与对照组无差异（P >0.05），而模型组、低剂量牛磺酸干预组大鼠穿越平台次数、目标象限停留时间均明显低于对照组（P <0.05）。对照组、模型组、低剂量和高剂量牛磺酸干预组大鼠海马CA1区神经细胞凋亡率分别为5.11%、18.87%、9.39%、4.63%，模型组大鼠海马CA1区神经细胞凋亡率高于对照组、低剂量和高剂量牛磺酸干预组（P <0.05）。低剂量和高剂量牛磺酸干预组大鼠海马中caspase 3、bax、bcl-2蛋白表达量与对照组相比均无差异（P >0.05）；而模型组大鼠海马中caspase 3、bax蛋白表达量均高于对照组、低剂量和高剂量牛磺酸干预组（P <0.05），bcl-2蛋白表达量低于对照组（P <0.05）。结论 甲醛及苯系物混合暴露会损害幼年大鼠的学习记忆能力，并增加海马CA1区神经细胞的凋亡；而牛磺酸可改善受损情况。
Abstract:Background Formaldehyde and benzene homologues are common environmental pollutants, and their neurotoxicity has aroused widespread concern.
Objective To investigate the effect of taurine on cognitive impairment after exposure to formaldehyde and benzene analogues in young rats.
Methods Twenty four-week old SD rats were randomly divided into four groups, with six rats in each group: control group (clean air), model group (5 mg·m−3 formaldehyde + 5 mg·m−3 benzene + 10 mg·m−3 toluene + 10 mg·m−3 xylene), low-dose taurine intervention group (5 g·L−1 taurine + mixture of formaldehyde and benzene analogues), and high-dose taurine intervention group (10 g·L−1 taurine + formaldehyde and mixture of benzene analogues), and the exposure was administered by oral and nasal aerosol inhalation for 28 d. At the end of exposure, the learning and memory ability of rats in each group was measured by Morris water maze test. After the behavioral test, the rats were anesthetized and neutralized, and the brain tissue was harvested for histopathological and molecular biological tests. The apoptosis rate of neurons in hippocampal CA1 area was detected by Tunel assay, and the expression levels of apoptosis-related proteins such as caspase 3, bax, and bcl-2 in hippocampal tissue were detected by Western blotting.
Results The growth and development of rats in each group were good during inhalation. During the Morris water maze experiment, the escape latencies of rats in the taurine intervention groups were not different from that in the control group (
P >0.05) from day 3 to day 5 of training, while the escape latency of rats in the model group was significantly higher than that in the control group (P <0.05). The number of crossing platform and the target quadrant residence time in the high-dose taurine intervention group were not different from those in the control group (P >0.05), while the two variables in the model group and low-dose taurine intervention group were significantly lower than those in the control group (P <0.05). The apoptotic rates of neurons in the hippocampal CA1 area of rats in the control group, model group, and low-dose and high-dose taurine intervention groups were 5.11%, 18.87%, 9.39%, and 4.63%, respectively. The apoptotic rate in the model group was higher than those in the control group and low-dose and high-dose taurine intervention groups (P <0.05). The expression levels of caspase 3, bax, and bcl-2 in the hippocampus of rats in the low-dose and high-dose taurine intervention groups showed no difference compared with the control group (P >0.05). The expression levels of caspase 3 and bax in the model group were higher than those in the control group and low-dose or high-dose taurine intervention groups (P <0.05), and the expression levels of bcl-2 was lower (P <0.05).Conclusion The mixed exposure to formaldehyde and benzene analogues can damage the learning and memory ability of young rats, and increase the apoptosis of neurons in hippocampal CA1 region. Taurine can reverse the damage induced by formaldehyde and benzene analogues.
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