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砷对大鼠脑海马c-fos、c-jun表达和细胞调亡影响

Effects of arsenic on expressions of c-fos,c-jun and cell apoptosis in rat hippocampus

  • 摘要: 目的 观察砷对大鼠脑海马区c-fos、c-jun蛋白表达和细胞凋亡影响,探索砷对大脑神经毒性机制。方法 将56只SD大鼠随机分成4组,即低、中、高剂量染砷组(亚砷酸钠:5、10、20 mg/kg)和对照组,染砷组灌胃染毒,对照组给予蒸馏水,连续15 d,处死大鼠;免疫组化法和DNA 断裂原位末端标记法(TUNEL)法分别测定大鼠脑海马区c-fos、c-jun蛋白表达和细胞凋亡指数。结果 低、中、高剂量组大鼠脑海马区c-fos、c-jun蛋白表达阳性率分别为(54.86±10.35)%、(64.18±6.23)%、(73.69±5.52)%和(0.434±0.044)%、(0.620±0.067)%、(0.711 ±0.026)%,细胞凋亡指数分别为(37.80±5.28)%、(48.49±5.25)%、(72.30±4.81)%,与对照组比较差异有统计学意义(P<0.01),且呈剂量-反应关系;经相关性分析显示,大鼠海马区c-fos、c-jun蛋白表达阳性率与细胞凋亡指数均呈正相关,c-fos与c-jun蛋白表达阳性率也呈正相关。结论 砷可诱导大鼠脑海马区c-fos、c-jun蛋白表达,促使细胞凋亡增加;过度的c-fos、c-jun表达可能是砷致大脑神经毒性的原因之一。

     

    Abstract: Objective To observe the effects of arsenic on the expressions of c-fos,c-jun and cell apoptosis in rat hippocampus,and to explore the neurotoxic mechanism of arsenic.Methods Fifty-six Sprague-Dawley(SD)rats were randomly divided into 4 groups:low-,medium-,and high-dose group(sodium arsenite:5,10 and 20 mg/kg)and the control group.The exposuse groups were exposed to sodium arsenite by intragastric admintration and the control group was treated with distilled water for 15 days,and then all the rats were sacrificed.The positive ratio of c-fos and c-jun expressions and index of cell apoptosis in rat hippocampus were determined with immunohistochemical and terminal deoxynuel eotidyl transferase-mediated dUTP nick end-labeling(TUNEL)method.Results The positive ratios of c-fos and c-jun expression in rat hippocampus of low-,medium- and high-dose groups were 54.86±10.35%,64.18±6.23%,and 73.69±5.52% and 0.434±0.044%,0.620±0.067%,and 0.711 ±0.026%,and the index of apoptosis was 37.80±5.28%,48.49±5.25%,and 72.30±4.81%,respectively,with significant differences compared with those of the control group (P<0.01 for all) and clear dose-response relationships.The correlation analysis demonstrated that the positive ratio of c-fos and c-jun expression in rat hippocampus in the three arsenic exposure groups correlated positively with the index of apoptosis,and the positive expression rate of c-fos was also positively correlated with that of c-jun.Conclusion The results demonstrate that arsenic promotes the expressions of c-fos and c-jun in rat hippocampus and leads to apoptosis of neuron.The overexpression of c-fos and c-jun in brain may be one of the reasons that results in neurotoxicity of arsenic.

     

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