中文摘要：

目的 探讨邻苯二甲酸（2-乙基己基）酯[di-2-ethylhexyl）phthalate,DEHP]对大鼠海马神经元树突和突触形态发育的影响。方法 体外培养5 d的新生大鼠海马神经元DEHP暴露5 d后,激光共聚焦显微镜下观察免疫荧光染色后的神经元,分析树突丝、树突棘和突触密度,采用Western blot法检测突触蛋白表达水平。结果0.10、1、10μmol/L DEHP显著下调体外培养海马神经元的树突丝、树突棘和突触密度;与对照组比较,1μmol/L DEHP组海马神经元树突丝、树突棘和突触密度[分别为（6.23±0.19）、（4.91±0.09）、（4.04±0.13）个/20μm]明显下降（P〈0.01）,该作用可被雌激素受体阻断剂ICI182,780部分消除（P〈0.01）;1μmol/L DEHP还可拮抗0.01μmol/L 17β-E2对树突和突触密度的促进作用（P〈0.01）;Western blot分析结果显示,与对照组比较,1μmol/L DEHP神经细胞突触蛋白synapsin I、PSD-95、N-甲基-D-天冬氨酸（NM DA）受体亚基NR2B、磷酸化胞外调节蛋白激酶（p-ERK）1/2表达[分别为（0.53±0.08）、（0.75±0.03）、（0.66±0.06）、（0.67±0.02）]明显降低（P〈0.01）。结论 DEHP可能由雌激素受体介导抑制大鼠海马神经元树突和突触形态发育,其机制可能与突触蛋白和NMDA受体表达水平下降及ERK1/2信号通路抑制有关。

英文摘要：

Objective To investigate the effect of di- （2-ethylhexyl） phthalate （DEHP） on dendritic and synaptic morphology of hippocampal neurons in rats. Methods Cultured hippocampal neorons of rats at day 5 in vitro were ex- posed to DEHP for 5 days. After immunofluorescence staining, the neurons were morphologically observed under confocal laser scanning microscope, and the densities of dendritic filopodia, dendritic spine and synapse were analyzed. Further- more,the expression level of synapsin was detected with Western blot. Results Exposures to DEHP at 100 nM, 1 IxM, and 10 txM for 5 days significantly reduced the densities of dendritic filopodia, spine, and synapse in the cultured hipp- ocampal neurons. Compared with the control, the densities of dendritic filopodia, spine, and synapse after DEHP treatment at 1μmol/L significantly reduced to 6. 23 ± 0. 19,4. 91 ± 0. 09, and 4.04 _± 0. 13/20 μm, respectively （ P 〈 0.01 for all）. However,the inhibitive effect was partly rescued by ICI 182,780, an inhibiter of estrogen receptor （P 〈 0. 01 ）. DEHP antagonized promotive effect of 1713-estradiol （ 17f3-E2 ） on the morphological development of dendrite and synapse when DEHP was combined with 1713-E2 （ P 〈 0. 01 ）. Furthermore, decreased expressions of synapsin I （ 0. 53 ± 0.08）, post synaptic density protein 95 （PSD-95） （0.75 ± 0.03 ）, N-methyl-D-aspartic acid （NMDA） receptor 2B sub- unit （NR2B） （0. 66 ± 0. 06 ）, and phosphorylated extracellular signal-regulated kinase （ERK） 1/2 （0. 67 ± 0. 02 ） were found after 1μM of DEHP treatment （P 〈 0. 01 for all）. Conclusion DEHP may inhibit the development of dendritic and synaptic morphology of hippocampal neurons in rats through estrogen receptors, and decreased expressions of synaptic proteins and NMDA receptors and the inhibition of ERK1/2 signaling may be involved in the inhibitions, suggesting that DEHP has a toxic effect on the development of neurons.