小檗碱对铝过负荷致小鼠慢性脑损伤的保护作用及机制

目的观察小檗碱对铝过负荷致大鼠慢性脑损伤的保护作用及机制。方法采用AlCl3(Al3 ,400mg/kg)ig大鼠,建立铝过负荷致大鼠慢性脑损伤的动物模型,并在每次铝给予4h后,小檗碱(100mg/kg)ig大鼠;观察大鼠行为学、组织病理学、生化酶学、单胺氧化酶-B(MAO-B)mRNA及蛋白表达水平变化。结果铝过负荷能明显导致大鼠被动回避性学习记忆能力和空间识别能力障碍、海马神经元损伤,使其脑组织乙酰胆碱转移酶(ChAT)活性显著降低,而胆碱脂酶(AchE)活性显著升高,超氧化物歧化酶(SOD)活性显著降低,而丙二醛(MDA)水平显著升高,MAO-B活性与MAO-BmRNA及蛋白表达水平显著增加;小檗碱能明显改善铝过负荷大鼠的学习记忆能力障碍,明显减轻铝过负荷大鼠海马神经细胞的损伤,明显阻遏铝过负荷大鼠海马组织ChAT与SOD活性的降低、AchE活性与MDA水平的增高、MAO-B活性及其mRNA与蛋白表达的增加。结论小檗碱对铝过负荷致大鼠慢性脑损伤有明显的保护作用,其作用机制除了与抗氧化应激损伤有关外,尚与增强胆碱能神经元功能与多巴胺神经功能有关。

Protection and mechanism of berberine against chronic brain injury induced by aluminum-overload in rats

Objective To study the protection and mechanism of berberine against chronic brain injury. Methods The chronic brain injury model of rats were established via intragastric administration of aluminum trichloride (400 mg/kg),and berberine (100 mg/kg) was intragastrically administered 4 h following the aluminum administration. The changes of behavior,histopathology,biochemical enzyme,and the expression of MAO-B mRNA,and protein in rat brain tissue were observed. Results Aluminum-overload could markedly induce impairments of avoidant learning and memory function,spatial distinguish function and injury of hippocampal neurons in rats,while ChAT activities significantly decreased but AchE activities increased,SOD activities significantly decreased but MDA contents increased,MAO-B activities,expression of MAO-B mRNA,and protein significantly increased in rat brain tissue. The administration of berberine could significantly prevent rats from the impairment of learning and memory function and hippocampal neuron injury,while significantly inhibit the decreasing of ChAT and SOD activities,the increasing of AchE activities,MDA contents,and MAO-B activities,and the expression of MAO-B mRNA and protein. Conclusion Berberine has an obvious protective effect against chronic brain injury. In addition to combating oxidative stress impairment,the mechanism of the protection is also related to enhancing the function of cholinergic and dopamine neurons.