目的 探讨纳米硫化铅和醋酸铅亚慢性经口染毒对大鼠脑组织中谷氨酸(Glu)、丝氨酸(Ser)、甘氨酸(Gly)和γ-氨基丁酸(GABA)等氨基酸类神经递质的影响。方法 无特定病原体级健康雌性SD大鼠随机分为对照组、醋酸铅组和纳米硫化铅组,每组15只。2个铅染毒组大鼠分别予给醋酸铅(100mg/kg体质量)和纳米硫化铅混悬液(10mg/kg体质量)灌胃,对照组予等体积质量分数为0.9%的氯化钠溶液灌胃,每周5次,连续12周。染毒结束处死大鼠,分离皮质和海马组织,采用电感耦合等离子体-质谱法测定铅水平,采用高效液相色谱法检测Glu、Ser、Gly和GABA水平。结果 醋酸铅和纳米硫化铅组大鼠皮质、海马组织内的铅水平均分别高于对照组(P〈0.05);纳米硫化铅组大鼠皮质和海马组织中的铅水平均低于醋酸铅组(P〈0.05),分别为醋酸铅组的48.8%和54.0%。与对照组比较,醋酸铅组和纳米硫化铅组大鼠的皮质、海马组织中Glu水平均升高,GABA和Gly水平均下降(P〈0.05);纳米硫化铅组大鼠皮质组织中Ser水平升高(P〈0.05),而海马组织中Ser水平下降(P〈0.05)。与醋酸铅组比较,纳米硫化铅组大鼠皮质组织中Glu和Ser水平均升高(P〈0.05),海马组织中的GABA水平下降(P〈0.05)。结论 纳米硫化铅和醋酸铅暴露均可导致大鼠脑组织内氨基酸类神经递质水平改变;纳米硫化铅暴露的影响较醋酸铅更为明显,这可能是其发挥神经毒性的毒理学机制之一。
Objective To investigate the effect of subchronic orally exposure to nano-size lead sulfide and lead acetate on amino acid neurotransmitters such as glutamate( Glu),Serine( Ser),Glycine( Gly) and γ-aminobutyric acid( GABA)in rat brain tissues. Methods Specific pathogen free healthy female SD rats were randomly divided into the control group,lead acetate group and nano-size lead sulfide group,with 15 rats in each group. Rats in both lead exposure groups were given 100 mg / kg body weight( bw) lead acetate or nano-size lead sulfide particles at dose of 10 mg / kg bw by gavage. Rats in the control group were given the same amount of 0. 9%( mass fraction) sodium chloride solution. All rats were treated5 times per week for 12 continuous weeks. Rats were scarified 24 hours after the last time of lead exposure. The brain cortex and hippocampus were taken. The lead level was determined by inductively coupled plasma-mass spectrometry. High performance liquid chromatography was used to detect the levels of Glu,Ser,Gly and GABA. Results The lead levels in cortex and hippocampus of lead acetate and nano-size lead sulfide exposed groups were significantly higher than those of the control group( P〈0. 05). Meanwhile,lead levels in cortex and hippocampus of nano-size lead sulfide group were lower than those of lead acetate group( P〈0. 05),which were 48. 8% and 54. 0% of lead acetate group respectively. Compared with control group,the Glu levels in cortex and hippocampus of lead acetate group and nano-size lead sulfide group increased,and the levels of Gly and GABA decreased( P〈0. 05); the Ser level in cortex of nano-size lead sulfide group was increased( P〈0. 05),while the Ser level in hippocampus decreased( P〈0. 05). Compared with lead acetate group,the Glu and Ser levels in cortex were increased( P〈0. 05),and GABA level in hippocampus was decreased in nano-size lead sulfide group( P〈0. 05). Conclusion Both nano-size lead sulfide and lead acetate exposure can le