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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、20mg/kg)和对照组,染砷组灌胃染毒,对照组给予蒸馏水,连续15d,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。
Objective To observe the effect of arsenic on c-fos, c-jun protein expression and apoptosis in hippocampus of rats and explore the mechanism of neurotoxicity of arsenic on brain. Methods 56 Sprague-Dawley rats were randomly divided into 4 groups: low, medium and high dose of arsenic (sodium arsenite: 5, 10, 20 mg / kg) and control group, The rats were sacrificed for 15 days. The expressions of c-fos and c-jun protein and apoptosis index in hippocampus of rats were determined by immunohistochemistry and TUNEL. Results The positive rates of c-fos and c-jun protein in hippocampus of rats in low, middle and high dose groups were (54.86 ± 10.35)%, (64.18 ± 6.23)%, (73.69 ± 5.52)% and (0.434 ± The apoptotic indexes were (37.80 ± 5.28)%, (48.49 ± 5.25)% and (72.30 ± 4.81)%, respectively, which were significantly lower than those of the control group (0.044%, 0.620 ± 0.067% and 0.711 ± 0.026% (P <0.01), and showed a dose-response relationship. The correlation analysis showed that there was a positive correlation between the positive rate of c-fos and c-jun protein expression and apoptosis index in hippocampus of rats, while c-fos And positive expression of c-jun protein was also positively correlated. Conclusions Arsenic can induce the expression of c-fos and c-jun proteins in the hippocampus of rats and promote the apoptosis of rat hippocampus. Over-expression of c-fos and c-jun may be one of the causes of arsenic-induced cerebral neurotoxicity.