目的:GJ-4是从中药栀子中提取分离出的一种藏红花色素富集物,本研究采用D-半乳糖联合亚硝酸钠所致亚急性衰老痴呆小鼠模型来评价GJ-4的学习记忆保护作用。方法:腹腔注射D-半乳糖(120mg·kg^-1)和亚硝酸钠(90 mg·kg^-1)诱导小鼠痴呆模型,同时各组小鼠分别灌胃(ig)给予GJ-4或阳性对照多奈哌齐以及脑复康,连续8周。采用跳台实验和Morris水迷宫检测小鼠行为学能力,并检测脑组织和血清中乙酰胆碱酯酶(Ach E)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)等相关指标,HE染色光镜下观察小鼠海马CA1区神经元变化。结果:与模型组比较,GJ-4组能明显缩短小鼠跳台潜伏期和减少跳台错误次数,延长小鼠在Morris水迷宫目标象限的游泳时间和增加穿越目标平台次数,表明GJ-4可提高亚急性衰老小鼠的学习记忆力和空间辨识能力。此外,GJ-4可降低脑组织中Ach E活性,保护海马CA1区神经元,并可不同程度提高血清及脑组织中SOD活性和GSH含量,降低MDA含量。结论:GJ-4对亚急性衰老痴呆小鼠的学习记忆能力有一定的保护作用,其作用机制可能与抑制Ach E和减少氧化应激损伤有关。
Objective: To evaluate the protective effect of GJ4, an extract from gardenia with saffron pigment enrichment, on learning and memory in mice with subacute senile dementia. Methods: The dementia was induced by intraperitoneal injection of D-galactose (120 mg·kg^-1) and nitrite sodium (90mg·kg^-1). The mice were intragastrically administered with GJ-4 or the positive controls donepezil and piracetam for 8 weeks. Then, the learning and memory abilities were evaluated by step-down test and Morris water maze test. Biochemical markers were also measured, such as acetylcholinesterase (ACHE) activity in the brain, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glntathione (GSH) content in the brain and blood. The pathological changes in hippocampus CA1 neurons were assessed by HE staining. Results: Compared with dementia control, GJ-4 prolonged step-down latency, and reduced number of errors in the platform; it also prolonged swimming time in the target quadrant, and increased number of times through the target platform. The results revealed that GJ-4 improved the learning and memory ability and spatial recognition ability of subacute aging mice. GJ-4 reduced AChE activity in the brain, protected neurons in the hippocampal CA1 region, increased the activities of SOD and the contents of GSH, and decreased the contents of MDA in the brain and serum. Conclusion: GJ4 has the protective effect on learning and memory ability in mice with subacute senile dementia, which may be associated with inhibition of AChE and reduction of oxidative stress.