多溴联苯醚-153对大鼠体内外神经细胞的毒性研究

发布时间：2018-05-09 05:11

本文选题：多溴联苯醚- + 神经毒性　；参考：《毒理学杂志》2015年01期

【摘要】：目的通过体内外实验,研究BDE-153对大鼠神经细胞的毒性损伤,为研究PBDE的神经毒性提供一定的科学依据。方法 (1)体内实验部分:将40只新生雄性清洁级SD大鼠按窝别和体重随机分为溶剂对照(橄榄油)组和低(1 mg/kg)、中(5 mg/kg)、高剂量(10 mg/kg)BDE-153染毒组,每组10只。在仔鼠出生第10天,采用一次性腹腔注射方式进行染毒,并且每周称重并记录大鼠的食欲、饮水量和体重增长状况,观察大鼠的神经行为变化。两个月后,在光镜和电镜下观察脑组织病理学形态和大鼠海马神经细胞超微结构以及TUNEL染色结果 ,采用比色法和流式细胞术分别检测LDH活力和细胞凋亡;(2)体外实验部分:体外培养大鼠原代神经元,分别用10、20和40μmol/L BDE-153染毒48 h后(另设DMSO溶剂对照组和空白对照组),在倒置显微镜下观察神经细胞的形态学改变,采用Hoechst 33258和AO/EB染色法观察BDE-153染毒后神经细胞凋亡,采用比色法、CCK-8试剂盒和流式细胞术分别检测LDH活力、细胞活力和神经细胞凋亡率。结果 (1)染毒后大鼠一般状况以及行为无明显改变。体内神经细胞病理形态学和超微结构观察显示,BDE-153能引起大鼠神经细胞形态发生改变。与对照组相比,体内外各染毒组海马神经细胞凋亡率和LDH活力均呈剂量依赖性地增加,差异有统计学意义(P0.05);(2)与对照组比较,体外各染毒组神经细胞的细胞活力呈现剂量依赖性地降低,差异有统计学意义(P0.05)。结论 BDE-153能引起体内外大鼠神经细胞的损伤,表现为细胞形态学和超微结构的改变,神经细胞活力降低,使细胞膜的通透性和细胞凋亡率增加。
[Abstract]:Objective to study the neurotoxicity of BDE-153 on rat nerve cells in vitro and in vivo, and to provide a scientific basis for studying the neurotoxicity of PBDE. Methods 1) in vivo experiment, 40 newborn male clean SD rats were randomly divided into solvent control group (olive oil) group, low dose group (olive oil), low dose group (1 mg / kg), middle dose group (5 mg / kg), high dose group (10 mg/kg)BDE-153), 10 rats in each group. On the 10th day of birth, rats were given a single intraperitoneal injection. The rats were weighed weekly and their appetite, drinking water and body weight were recorded, and the neurobehavioral changes of the rats were observed. Two months later, the histopathological morphology, ultrastructure of hippocampal neurons and TUNEL staining were observed under light and electron microscopy. Colorimetric assay and flow cytometry were used to detect LDH activity and apoptosis in vitro. After exposure to 10 渭 mol/L BDE-153 for 48 h (DMSO solvent control group and blank control group), the morphological changes of nerve cells were observed under inverted microscope. The apoptosis of neurons was observed by Hoechst 33258 and AO/EB staining. LDH activity, cell viability and neuronal apoptosis rate were detected by colorimetric assay with CCK-8 kit and flow cytometry, respectively. Results 1) there were no significant changes in general status and behavior of rats after exposure. Histopathological and ultrastructural observation of nerve cells in vivo showed that BDE-153 could induce morphologic changes of nerve cells in rats. Compared with the control group, the apoptosis rate and LDH activity of hippocampal neurons were increased in a dose-dependent manner in vivo and in vitro, and the difference was statistically significant (P 0.05) compared with the control group. In vitro, the cell viability of each exposed group decreased in a dose-dependent manner, and the difference was statistically significant (P 0.05). Conclusion BDE-153 can induce neuronal damage in rats in vivo and in vitro, which is characterized by the changes of cell morphology and ultrastructure, the decrease of neuronal activity, and the increase of cell membrane permeability and apoptosis rate.
【作者单位】：山西医科大学公共卫生学院;
【基金】：国家自然科学基金项目(81001258) 山西省优秀青年学术带头人支持计划(晋教财[2011]205号) 山西省基础研究计划项目(2013021033-3)
【分类号】：R114

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