目的探讨慢性铝染毒致大鼠神经细胞凋亡及P53磷酸化的变化。方法40只雄性SD大鼠按照体重随机分为空白对照组和低、中、高剂量AlCl3染毒组(每组10只),染毒剂量依次为10.73、107.33、1073.33mg/kg,染毒期6个月。染毒组将氯化铝(AlCl3·6H2O)混入饲料中喂养大鼠,对照组无AlCl3饲料饲养。TUNEL法检测大鼠皮质神经细胞凋亡,免疫印迹法检测大鼠皮质P53蛋白及其ser15位点磷酸化蛋白表达。结果低、中、高剂量组皮质神经细胞凋亡率均明显高于对照组,差异有统计学意义(P〈0.01)。随着染毒剂量的增加,大鼠脑皮质组织中P53和ser15位点磷酸化P53蛋白表达均增加。高剂量组P53蛋白表达量明显高于对照组和低剂量组,差异有统计学意义(P〈0.05);中、高剂量组ser15位点磷酸化P53蛋白的表达量明显高于对照组和低剂量组,差异有统计学意义(P〈0.05)。结论慢性AlCl3染毒可致大鼠皮质神经元P53及磷酸化P53蛋白表达增加,这可能是引起神经细胞凋亡的机制之一。
Objective To explore the role of P53 phosphorylation in neuron apoptosis of rats by chronic aluminum exposure. Methods A total of male 40 SD rats were divided randomly into 4 groups (n= 10/dose), the exposed groups were fed with normal diet with different concentration of AlCl3" 6H20 for 6 months respectively. The dosage of low, middle and high groups were 10.73,107.33,1073.33 mg/kg in sequence. The control group received normal diet. The neuron apoptosis was measured by method of Tunel. The expressions of P53 and pP53- ser15 protein in the cortex were detected by Western-blot. Results Tunel staining showed that the low,middle and high group rats had increased apoptosis rate than control group (P〈0.01).Western-blot test demonstrated that the expression of P53 protein in the cortex of high group rats were significantly higher than the control and low groups(P〈0.05 ). The expression of pP53-ser15 protein in the cortex of middle and high group rats were also higher than the control and low groups (P〈0.05). Conclusion Chronic aluminum exposure can lead to over expression of P53 and pP53-ser15 protein in cerebral cortex,which maybe one of the most important mechanisms of neuron apoptosis induced by AlCl3.