尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响研究

目的:探讨尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响。方法:取小鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和尼莫地平高、中、低(80、40、20mg.kg-1)剂量组,每组35只,后4组脑室内注射0.25氯化铝2μL,每天1次,连续5d,建立神经元退行性变小鼠模型,假手术组注射等体积人工脑脊液;5d后各组灌胃给予相应药物,每天2次,连续30d,末次灌胃24h后观察其脑组织的病理学变化,考察海马组织中丙二醛(MDA)、血红素加氧酶-1(HO-1)蛋白、铝离子和铁离子水平变化。结果:与模型组比较,尼莫地平高剂量组神经元损伤明显减轻,其中MDA、HO-1蛋白和铁离子水平明显降低(P<0.05);其余指标及尼莫地平中、低剂量组各项指标均无明显变化。结论:尼莫地平可能通过抑制HO-1蛋白表达维持铁离子代谢平衡,发挥缓解神经元退行性变的作用。

Effect of Nimodipine on Ferri Ion in Cerebral Tissue of Rats with Neurodegenerative Disease

OBJECTIVE： To investigate the effect of nimodipine on ferri ion in cerebral tissue of rats with neurodegenerative disease. METHODS： Mice were randomly divided into sham operation group （normal saline）, model group （normal saline）, nimodipine high-dose, medium-dose and low-dose groups （80, 40, 20 mg.kg^-1）, with each group of 35 mice. The latter 4 groups received 0.25% aluminum chloride 2 μL intracerebroventricularly once a day for five days to induce neurodegenerative model. Artificial cerebrospinal fluid 2 μL was injected in the same way in sham operation group. Five days later, all groups were given relevant medicine intragastrically twice a day for 30 d. Histological observations was performed 24 h after last intragastical injection to evaluate the levels of MDA, Heme oxygenase-1 （HO-1）, aluminium ion, ferri ion. RESULTS： Compared with model group, neural damage, MDA, HO-1 protein and ferri ion level of nimodipine high-dose group were decreased significantly （P〈0.05）. Other index and all index of nimodipine medium-dose and low-dose groups had no different change. CONCLUSIONS： Nimodipine could suppress the neurodegenerative development through inhibiting the expression of HO-1 and keeping the balance of ferri ion metabolism.