目的探讨1,2-二氯乙烷(1,2-DCE)亚急性经口染毒对大鼠血浆中髓鞘碱性蛋白(MBP)、神经元特异性烯醇化酶(NSE)及S100蛋白影响。方法无特定病原体级成年SD大鼠随机分为对照、低和高剂量组,每组16只,雌雄各半,分别给予剂量0、27和79 mg/kg体质量的1,2-DCE隔日灌胃染毒,共4周。染毒后各组随机抽取8只存活大鼠(雌雄各半),以酶联免疫吸附法检测血浆中MBP、NSE和S100蛋白水平,以气相色谱法检测尿和血浆中1,2-DCE及其主要代谢产物2-氯乙酸、2-氯乙醛和2-氯乙醇水平;分离大鼠大脑和小脑,光学显微镜下观察其病理变化,免疫组织化学法检测大脑和小脑组织中MBP表达情况。结果染毒期间,高剂量组大鼠染毒第3天出现活动异常,共死亡6只(雌性2只,雄性4只);低剂量组和对照组大鼠未见活动异常和死亡。高剂量组大鼠血浆中MBP水平高于对照组(P〈0.05);3组大鼠血浆中NSE和S100蛋白水平比较,差异均无统计学意义(P〉0.05)。高剂量组大鼠尿中检出1,2-DCE和2-氯乙醇,低剂量组和对照组均未检出;高剂量组大鼠尿中2-氯乙酸水平高于低剂量组(P〈0.05),对照组大鼠尿中未检出2-氯乙酸;3组大鼠尿中均未检出2-氯乙醛,血浆中均未检出1,2-DCE及其3种代谢产物。大脑、小脑皮质和白质组织病理学检查未见明显结构性异常,未见明显出血、水肿及坏死。在大鼠大脑侧脑室和小脑第四脑室脉络丛上皮细胞中,相较于对照组,低剂量组MBP表达稍增强,高剂量组MBP表达明显增强。结论 MBP可能在1,2-DCE的毒性作用机制中发挥一定作用。
Objective To investigate the effects of 1,2-dichloroethane( 1,2-DCE) on myelin basic protein( MBP),neuron specific enolase( NSE) and S100 protein in the plasma of SD rats. Methods Forty-eight specific pathogen free adult SD rats were randomly divided into control group,low-dose group and high-dose group,with 8 females and 8 males in each group. Rats were given 1,2-DCE orally at the dose of 0,27 and 79 mg / kg body weight every other day( every Wednesday,Monday and Friday) for 4 weeks. After 1,2-DCE administration,8 survived rats( half male and female) were randomly selected in each group. The plasma levels of MBP,NSE and S100 protein were measured using enzyme-linked immunosorbent assay. The blood and urinary samples were collected to assess the concentration of 1,2-DCE and its main metabolites( 2-chlorideacetic acid, 2-chlorideacetaldehyde and 2-chlorideethanol) by gas chromatography. The pathological changes of cerebrum and cerebellum were observed through optical microscope,and the expression of MBP was detected by immunohistochemistry. Results Rats in high-dose group showed abnormal behavior from the third day of1,2-DCE exposure and 6 rats( 2 females,4 males) died from 1,2-DCE intoxication. Rats in low-dose group and control group appeared normal and no death was observed. MBP level in the plasma of high-dose group was higher than that in the control group( P〈0. 05),but the levels of NSE and S100 protein in each group did not show significant statisticaldifference( P〈0. 05). 1,2-DCE and 2-chloroethanol in the urine were detected in the high-dose group,and were below detection limit in the other two groups. 2-Chloroacetic acid level in high dose-group was significantly higher than that in the low-dose group( P〈0. 05),and was below detection limit in the control group. 2-Chloroacetaldehyde in the urine of each group was below detection limit. 1,2-DCE and its 3 kinds of metabolites were not detected in the plasma of all rats. There was no obvious structural damage,bl