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衰老细胞清除剂可预防雌性小鼠大脑的与年龄相关变化。

Senolytics prevent age-associated changes in female mice brain.

机构信息

Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil.

Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário S/N, Pelotas, RS, Brazil.

出版信息

Neurosci Lett. 2024 Mar 15;826:137730. doi: 10.1016/j.neulet.2024.137730. Epub 2024 Mar 12.

DOI:10.1016/j.neulet.2024.137730
PMID:38485080
Abstract

PURPOSE

Considering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer's disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na, K-ATPase activities in brain of female mice.

METHODS

Female C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age.

RESULTS

Results indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na, K-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction.

CONCLUSION

These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.

摘要

目的

鉴于达沙替尼和槲皮素(D+Q)联合具有神经保护作用,并且女性在衰老过程中经历激素水平下降,这与阿尔茨海默病的易感性增加有关,因此在本研究中,我们评估了 D+Q 对雌性小鼠大脑中炎症和氧化应激标志物以及乙酰胆碱酯酶和 Na、K-ATP 酶活性的影响。

方法

将 C57BL/6 雌性小鼠分为对照组和 D(5mg/kg)+Q(50mg/kg)治疗组。治疗通过灌胃给药,每两周连续给药 3 天,从 30 天龄开始。动物在 6 个月和 14 个月大时被安乐死。

结果

结果表明,随着年龄的增长,对照组动物大脑中的活性物质(RS)、巯基含量和脂质过氧化增加,随后亚硝酸盐水平和超氧化物歧化酶、过氧化氢酶和谷胱甘肽 S-转移酶活性降低。D+Q 可防止与年龄相关的 RS 增加和过氧化氢酶活性降低。乙酰胆碱酯酶活性增加,而 Na、K-ATP 酶活性在 14 个月时降低,D+Q 可防止这种降低。

结论

这些数据表明,D+Q 可以防止雌性大脑中与年龄相关的神经化学改变。

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