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目的研究钙结合蛋白-D28K(CaBP)对脑内多巴胺(DA)能神经细胞的保护作用。方法测定CalbindinD-28k转基因小鼠黑质致密部、腹侧被盖区、海马的CaBP和黑质致密部CaBP阳性细胞数,注射1-甲基-4苯基-1,2,3,6-四氢吡啶(MPTP),建立帕金森病(PD)模型,通过模型鼠游泳、悬挂、移动能力等行为学指标以及黑质致密部酪氨酸羟化酶(TH)阳性细胞数来测定过表达CaBP抗MPTP对DA能神经细胞的损伤能力。结果转基因鼠黑质致密部、腹侧被盖区CaBP量显著高于正常鼠,海马、大脑皮层中CaBP量与正常组相比无明显差异。黑质致密部CaBP阳性细胞数显著高于正常小鼠[(140±9.89)个vs(101±7.82)个]。MPTP造模后,转基因鼠黑质致密部TH阳性细胞数和4项行为学变化差异不显著,而正常鼠造模后鼠黑质致密部TH阳性细胞数和4项行为学变化差异显著。结论过表达的CaBP对脑内DA神经细胞具有保护作用。
Objective To study the protective effect of calcium-binding protein-D28K (CaBP) on dopaminergic neurons in the brain. Methods The number of CaBP-positive cells in the substantia nigra pars compacta, ventral tegmental area, CaBP and substantia nigra pars compacta in Calbindin D-28k transgenic mice were measured. The number of CaBP-positive cells in the substantia nigra pars compacta injected with 1-methyl-4-phenyl- Tetrahydropyridine (MPTP) was used to establish a model of Parkinson’s disease (PD). Overexpression of tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta was determined by behavioral indexes such as swimming, CaBP anti-MPTP damaging ability of DA neurons. Results The amount of CaBP in substantia nigra pars compacta and ventral tegmental area in transgenic mice was significantly higher than that in normal rats, hippocampus and cerebral cortex. The number of CaBP positive cells in substantia nigra pars compacta was significantly higher than that in normal mice [(140 ± 9.89) vs (101 ± 7.82)]. After MPTP modeling, there was no significant difference in the TH positive cells and behavioral changes among the substantia nigra pars compacta of transgenic mice, while there were significant differences in the number of TH positive cells and the four behavioral changes in the substantia nigra pars compacta of normal mice. Conclusion Overexpression of CaBP has a protective effect on DA neurons in the brain.