ABSTRACT
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,bleeding,edema or necrosis found in the cortex and white matter of cerebrum and cerebellum. The expression of MBP in the choroid plexus epithelial cells were significantly enhanced in the lateral ventricle and the fourth ventricle of rats in the high-dose group,and slight enhanced in rats in the low-dose group. CONCLUSION: MBP may play a role in the toxic effect of 1,2-DCE.
ABSTRACT
OBJECTIVE: To explore the effects of aquaporin 4( APQ4) in rat toxic brain edema induced by subacute 1,2-dichloroethane( 1,2-DCE) exposure. METHODS: Thirty-two specific pathogen free healthy adult female SD rats were randomly divided into control( 8 rats),low-dose( 12 rats) and high-dose( 12 rats) groups. The treatment groups were exposed to 1,2-DCE( low-dose: 600 mg / m3; high-dose: 1 800 mg/m3,nose-only) and the control group was exposed to fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After exposure,histopathologic changes were examined in the cerebral cortex. Real-time polymerase chain reaction was used to detect the mRNA relative expression of matrix metalloproteinase 2( MMP2),Na-K-Cl cotransporter-1( NKCC1) and AQP4. The Western blotting was used to detect the expression of AQP4 protein in the cerebral cortex. RESULTS: The pathological results showed that the cerebral cortex tissues were loose around the peripheral vessels and the vessels tissue space appeared widen in low-dose exposure group. The pathological change was more serious in high-dose group than low-dose group,with obvious loosen vessels and vacuole. Compared with those of the control group and the low-dose group,the relative expression level of MMP2 mRNA in the high-dose group increased significantly[( 1. 07 ± 0. 41) vs( 1. 56 ± 0. 55),( 1. 21 ± 0. 59) vs( 1. 56 ± 0. 55),P <0. 05],while the the relative expression level of AQP4 mRNA in the high-dose group significantly decreased [( 1. 03 ±0. 25) vs( 0. 81 ± 0. 12),( 1. 00 ± 0. 20) vs( 0. 81 ± 0. 12),P < 0. 05]. The relative expression levels of NKCC1 mRNA in all groups showed no statistical difference [( 1. 03 ± 0. 31) vs( 1. 14 ± 0. 43) vs( 1. 36 ± 0. 50),P > 0. 05]. The relative expression level of AQP4 protein in the high-dose group was lower than that of the control group [( 0. 80 ± 0. 25) vs( 1. 19 ± 0. 42),P < 0. 05]. CONCLUSION: The brain edema induced by subacute inhalation of 1,2-DCE is of mixed types with vasogenic edema as its main symptom. Its pathogenesis is related to the changes of AQP4 expression.