论文部分内容阅读
目的探讨2,2’,4,4’-四溴联苯醚(PBDE-47)和2,2’,4,4’,5,5’-六氯联苯(PCB153)单独或联合染毒对SD大鼠的神经毒性作用及其机制。方法出生第10 d的SD大鼠经一次性PBDE-47[1,5,10 mg/(kg.bw)]和/或PCB153[5 mg/(kg.bw)]染毒,用Morris水迷宫试验观察2月龄大鼠空间学习、记忆能力;用实时荧光定量RT-PCR检测海马组织死亡相关蛋白激酶(DAPK)、X染色体连锁的凋亡抑制蛋白(XIAP)、含半胱氨酸的天冬氨酸酶-12(Caspase-12)、含半胱氨酸的天冬氨酸酶-3(Caspase-3)以及细胞色素(cytochrome C)等钙信号通路相关基因mRNA的表达水平。结果随PBDE-47染毒剂量的增加,大鼠学习、记忆能力呈现减退的趋势,且所有染毒剂量组与对照组比较差异均有统计学意义(P<0.05),PCB153可增加PBDE-47的神经毒性作用。与对照组比较,10 mg/(kg.bw)染毒组PBDE-47可导致雌雄大鼠XIAP基因mRNA表达水平显著下调(P<0.05),同时使雌雄大鼠Caspase-12、Caspase-13、Cytochrome C以及雄性大鼠DAPK基因mRNA表达水平显著上调(P<0.05)。除雌雄大鼠DAPK以及雌性大鼠Cyto-chrome基因外,PBDE-47和PCB153对雌雄大鼠其他各基因mRNA表达水平的影响具有交互作用(P<0.05)。结论PBDE-47可引起大鼠神经系统损伤,同时影响大鼠海马区钙信号诱导的凋亡相关基因mRNA表达水平,PCB153可增强PBDE-47的上述神经毒性作用。
Objective To investigate the effects of 2,2 ’, 4,4’-tetrabromodiphenyl ether (PBDE-47) and 2,2’, 4,4 ’, 5,5’-hexachlorobiphenyl (PCB153) alone or in combination Neurotoxic effect on SD rats and its mechanism. Methods SD rats on the 10th day of gestation were exposed to either PBDE-47 [1,5,10 mg / (kg.bw)] and / or PCB153 [5 mg / (kg.bw)] once, The spatial learning and memory abilities of 2-month-old rats were observed. The changes of death-associated protein kinase (DAPK), X-linked inhibitor of apoptosis (XIAP) and cysteine- Caspase-12, Caspase-3, and cytochrome C were detected by flow cytometry. Results With the increase of PBDE-47 dose, the learning and memory abilities of rats decreased gradually, and the difference was statistically significant (P <0.05) between all dose groups and control group. PCB153 increased PBDE-47 The neurotoxic effect. Compared with the control group, PBDE-47 induced a significant decrease in mRNA expression of XIAP in both male and female rats (P <0.05), and at the same time, caspase-12, Caspase-13, Cytochrome C and DAPK mRNA expression in male rats were significantly up-regulated (P <0.05). Except male and female DAPK and female Cyto-chrome genes, PBDE-47 and PCB153 had interaction effects on mRNA expression of other genes in both male and female rats (P <0.05). Conclusion PBDE-47 can induce the damage of the nervous system and the mRNA expression of apoptosis-related genes induced by calcium signal in the hippocampus of rats. PCB153 can enhance the neurotoxicity of PBDE-47.