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目的探讨1-溴丙烷(1-BP)亚急性吸入染毒对雄性大鼠血浆和脑组织中神经元特异性烯醇化酶(NSE)和髓鞘碱性蛋白(MBP)的影响。方法无特定病原体级成年雄性Wistar大鼠随机分为对照组和低、中、高剂量组,每组12只,分别予质量浓度为0、1 250、2 500、5 000 mg/m3的1-BP连续动式吸入染毒,每天染毒6 h,每周5 d,连续4周。染毒结束后,各组随机取9只大鼠,经腹主动脉采血,分离血浆,采用免疫酶联吸附法检测其NSE和MBP水平,分离全脑、大脑、小脑和脑干检测脏器系数;各组另3只大鼠行脑病理组织学检查,并采用免疫组织化学法检测脑组织中NSE和MBP的蛋白表达。结果高剂量组大鼠全脑、大脑、小脑及脑干的脏器系数分别高于对照组[(0.754±0.056)%vs(0.663±0.035)%,(0.382±0.037)%vs(0.339±0.021)%,(0.115±0.008)%vs(0.098±0.006)%,(0.213±0.018)%vs(0.183±0.014)%,P<0.01]。低、中和高剂量组大鼠血浆中NSE水平分别低于对照组[(7.92±0.53)vs(24.73±11.44)mg/L,(9.12±2.17)vs(24.73±11.44)mg/L,(11.10±2.84)vs(24.73±11.44)mg/L,P<0.01];4组大鼠血浆中MBP水平比较,差异无统计学意义[(2.52±0.70)vs(2.50±0.72)vs(2.47±0.66)vs(2.44±0.81)mg/L,P>0.05]。脑组织病理学检查结果显示:仅在高剂量组大鼠大脑海马区观察到少量坏死的神经元。低、中剂量组和对照组大鼠脑组织中NSE、MBP的蛋白表达量无明显差异,仅在高剂量组大鼠大脑海马区观察到NSE和MBP蛋白表达量下调的细胞。结论 1-BP所致的神经毒性对中枢神经功能影响比结构影响更为明显;血浆中NSE可能是1-BP暴露的效应标志物之一。
Objective To investigate the effects of 1-bromopropane (1-BP) subacute inhalation on neuron-specific enolase (NSE) and myelin basic protein (MBP) in plasma and brain of male rats. Methods Adult male Wistar rats without specific pathogen were randomly divided into control group and low, medium and high dose group, 12 rats in each group. The rats were randomly divided into 1-, 2-, 2-, BP continuous dynamic inhalation exposure, daily exposure to 6 h, 5 d per week for 4 weeks. After the treatment, nine rats in each group were randomized to take blood through the aorta to separate the plasma. The levels of NSE and MBP were detected by enzyme-linked immunosorbent assay (ELISA), and the organ coefficients of whole brain, cerebrum, cerebellum and brain stem . The other three rats in each group were subjected to brain histopathological examination. The protein expression of NSE and MBP in brain tissues was detected by immunohistochemistry. Results The organ coefficients of whole brain, cerebrum, cerebellum and brain stem in high dose group were significantly higher than those in control group [(0.754 ± 0.056)% vs (0.663 ± 0.035)%, (0.382 ± 0.037)% vs (0.339 ± 0.021 )%, (0.115 ± 0.008)% vs (0.098 ± 0.006)%, (0.213 ± 0.018)% vs (0.183 ± 0.014)%, P <0.01]. The plasma levels of NSE in the low, middle and high dose groups were lower than those in the control group [(7.92 ± 0.53) vs (24.73 ± 11.44) mg / L, (9.12 ± 2.17) vs (24.73 ± 11.44) mg / L, 11.10 ± 2.84 vs 24.73 ± 11.44 mg / L, respectively, P <0.01]. There was no significant difference in plasma MBP levels between the 4 groups ([2.52 ± 0.70] vs (2.50 ± 0.72 vs 2.47 ± 0.66) vs (2.44 ± 0.81) mg / L, P> 0.05]. Brain histopathological examination showed that only a small amount of necrotic neurons were observed in hippocampus of high-dose group rats. There was no significant difference in the expression of NSE and MBP in the brain tissue of low, medium and control rats. Only the cells with high expression of NSE and MBP were observed in hippocampus of high-dose group. Conclusion The neurotoxicity induced by 1-BP may have a more significant effect on the central nervous system than the structure. NSE in plasma may be one of the effect markers of 1-BP exposure.