A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2
A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2
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DOI：
10.1111/j.1742-7843.2007.00138.x
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发表时间：
2007-12-01
影响因子：
3.1
通讯作者：
Liu, Gengtao
中科院分区：
文献类型：
--
作者：
Fang, Fang;Liu, Gengtao
本研究旨在探讨新合成的角酰胺环类似物化合物FLZ对慢性注射d -半乳糖和亚硝酸钠（NaNO2）诱导的人工衰老小鼠记忆损伤的保护作用。通过连续注射d -半乳糖（120 mg/kg）和NaNO2 (90 mg/kg)，每天1次，连续60 d，建立人工衰老小鼠模型。复方FLZ（75和150 mg/kg）在d -半乳糖和NaNO2注射30天后口服，每天1次，连用30天。采用水迷宫法评价小鼠的学习记忆功能。采用不同生化试剂盒测定大鼠血清丙二醛（MDA）含量、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性。光镜、电镜观察海马形态变化。免疫组化染色法计数海马组织Bcl-2免疫反应细胞，Western blot法分析Bcl-2蛋白表达。结果表明，注射d -半乳糖和NaNO2可引起小鼠海马记忆损伤和神经元损伤。血清SOD和GSH-Px活性降低，MDA水平升高。海马Bcl-2阳性神经元及Bcl-2蛋白表达显著降低。口服FLZ 30 d可显著改善小鼠认知功能缺损及上述生化指标，并可减轻小鼠海马的病理改变。结果表明，FLZ可改善慢性注射d -半乳糖和NaNO2诱导的人工衰老小鼠的记忆缺陷和病理损伤，表明FLZ在抗衰老和抗痴呆方面值得进一步研究。
The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO2). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO2 (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO2 injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO2 induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO2, indicating that FLZ is worth further studies for fighting antisenescence and dementia.