饮水途径慢性砷染毒大鼠坐骨神经髓鞘结构和功能的变化

Impact of the chronic arsenic exposure through drinking water on myelin sheath structure and function of sciatic nerve in rats

目的探讨慢性砷染毒对大鼠坐骨神经髓鞘结构和功能的影响。方法将60只健康4周龄SPF级雄性SD大鼠随机分为3组,分别为对照(蒸馏水)组和2.5、10 mg/kg亚砷酸钠染毒组,每组20只。采用自由饮水方式进行染毒,连续6个月。测定大鼠坐骨神经的电生理指标以及N-乙酰神经氨酸的含量和β-半乳糖苷酶的活力。采用Western Blot法检测大鼠坐骨神经中髓鞘碱性蛋白(myelin basic protein,MBP)的表达水平。结果与对照组比较,10 mg/kg亚砷酸钠染毒组大鼠坐骨神经干动作电位幅度和传导速度均下降,而2.5 mg/kg亚砷酸钠染毒组大鼠坐骨神经干动作电位持续时间延长,差异均有统计学意义(P<0.05);各剂量亚砷酸钠染毒组大鼠坐骨神经干动作电位潜伏期和峰值期均无明显改变。且随着染毒剂量的升高,大鼠神经干动作电位的幅度和传导速度均呈下降趋势,而潜伏期呈上升的趋势,持续时间和峰值期均呈先升高后下降的趋势。与对照组相比,10 mg/kg亚砷酸钠染毒组大鼠坐骨神经中β-半乳糖苷酶的活力和MBP蛋白的表达水平均增加,而N-乙酰神经氨酸的含量降低,差异均有统计学意义(P<0.05)。且随着亚砷酸钠染毒剂量的升高,大鼠坐骨神经中β-半乳糖苷酶活力和MBP蛋白的表达水平均呈上升趋势,而N-乙酰神经氨酸的含量呈下降趋势。结论砷暴露可降低神经节苷脂的含量,增加MBP蛋白的表达,从而诱发周围神经毒性,这可能是砷中毒致周围神经病变的机制之一。

Objective To explore the effect of chronic arsenic exposure on myelin sheath structure and function of sciatic nerve in rats. Methods Sixty healthy male SD rats of SPF grade （4-week old） were randomly divided into three groups, 20 in each, control （distilled water） group and 2.5, 10 mg/kg body weight NaAsO2 expoure groups. The treatments were conducted by free drinking water for six consecutive months. The electrophysiological parameters of the sciatic nerve and the content of N- acetylneuraminic acid and the activity of β-galactosidase were measured. The expression changes of myelin basic protein （MBP） in sciatic nerve were tested by Western blot. Results Compared with the control group, the amplitude and conduction velocity of the sciatic nerve action potential were decreased in the 10 mg/kg NaAsO2 expoure group, and the duration of sciatic nerve action potential were prolonged in 2.5 mg/kg NaAsO2 expoure group （P〈0.05）. There was no obvious change in latency and peak period of sciatic nerve action potential between the NaAsO2 expoure groups. With the increase of exposure doses and exposure time, the amplitude and conduction velocity of the nerve action potentials decreased, while the latency period increased, and the duration and peak period increased first, then decreased. Compared with the control group, the activity of β- galactosidase and the protein expression of MBP were increased in the 10 mg/kg NaAsO2 expoure group, while the content of N-acetylneuraminic acid were decreased （P〈0.05）. With the increase of exposure doses and exposure time, the activity of β-galactosidase and the protein expression of MBP in the sciatic nerve increased, while the content of N-acetylneuraminic acid decreased. Conclusion Arsenic exposure can produces peripheral nerve toxicity by reducing the content of ganglioside and increasing the expression of myelin basic protein,which may be involved in the mechanisms of peripheral neuropathy caused by arsenic poisoning.