尼莫地平抗急性铅染毒大鼠海马神经元损伤的形态学研究

Morphological study of protecting effect of nimodipine on hippocampal neurons in rats acutely exposed to lead

目的:了解尼莫地平对急性铅染毒大鼠海马神经元损伤的干预作用。方法:48只2月龄SD大鼠随机等分为4组,即染铅组(40 mg/kg PbAc)、尼莫地平组(1 mg/kg Nim)、铅-尼莫地平组(40 mg/kg PbAc+1 mg/kg Nim)和对照组(等量生理盐水),每日腹注1次,连续3 d。用TUNEL法原位检测海马神经元凋亡情况,并用电镜观察海马神经元超微结构变化。结果:各组海马神经元凋亡指数由高到低依次为染铅组、铅-尼莫地平组、对照组和尼莫地平组,染铅能显著增高海马神经元凋亡指数(P<0.01),尼莫地平与铅存在交互作用(P<0.01),在铅染毒的前提下,尼莫地平能明显降低神经元凋亡指数。电镜观察显示,染铅组海马神经元有核固缩现象,而铅-尼莫地平组神经元未见明显异常。结论:急性铅染毒能引起海马神经元损伤,促进细胞凋亡;尼莫地平可能具有抗急性铅染毒海马神经元损伤的作用。

Objective： To study the protective effect of nimodipine （NIM） on hippocampal neurons in rats acutely exposed to lead （Pb）. Methods： 48 rats of 2 months old were randomly divided into four groups： Pb group （40 mg/kg PbAc）, NIM group （1 mg/kg Nim）, Pb-NIM group （40 mg/kg PbAc ＋ 1 mg/kg Nim） and control group. The treating rats were respectively administered intraperitoneally with lead acetate or/and nimodipine qd for 3 days. The control rats were given equal volume of 0.9% saline. The hippocampus was removed for electron microscopic examination and the neuron apoptosis was tested by TUNEL method. Results：The index of neuron apoptosis in hippocampus varied among different groups. The order of apoptosis index was as follow： Pb group〉Pb-NIM group〉control group〉NIM group. The rats exposed to lead significantly enhanced the neuron apoptosis （P〈0.01）. There was significant interaction on the neuron apoptosis between factors of Pb and NIM （P〈0.01）. Under exposure to lead, nimodipine could significantly reduce the index of neuronapoptosis. Electron microscopy showed that degenerative changes, such as pyknosis occurred in hippocampal neurons of Pb group. But there were no obviously degenerative changes observed in hippocampal neurons of Pb-NIM group. Conclusion：Acute exposure to lead may damage hippocampal neurons and then induce morphological changes such as apoptosis. Nimodipine may have protective effects on degenerative hippocampal neurons induced by acute lead poisoning.