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槲皮素纳米植物脂质体对母体分离模型中自闭症样损伤的预防作用:半胱天冬酶-3、Bax/Bcl-2和Nrf2的可能作用

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2.

作者信息

Moghaddam Akbar Hajizadeh, Eslami Ali, Jelodar Sedigheh Khanjani, Ranjbar Mojtaba, Hasantabar Vahid

机构信息

Department of Animal Sciences, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

Department of Animal Sciences, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.

出版信息

Behav Brain Res. 2023 Mar 12;441:114300. doi: 10.1016/j.bbr.2023.114300. Epub 2023 Jan 12.

Abstract

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg). Pups exposed to MS for 3 h per day from postnatal days (PND) 1-9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40 mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40 mg/kg) treated (p < 0.01). QNP treatment (10 and 40 mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p < 0.001), lipid peroxidation (p < 0.001), and increased catalase (CAT) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.001) activity, and glutathione (GSH) levels (p < 0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p < 0.001), but increased Bcl-2, and Nrf2 expressions (p < 0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

摘要

自闭症是一种在3岁前开始的神经元发育异常,表现为行为缺陷。本研究旨在制备载槲皮素纳米植物脂质体(QNP),以研究其对母体分离(MS)所致自闭症样模型中行为缺陷、小脑氧化应激和细胞凋亡的影响。新生大鼠随机分为七组,包括对照组、阳性对照组、疾病组,以及用槲皮素(10和40mg/kg)和QNP(10和40mg/kg)治疗的疾病组。与对照组相比,从出生后第1天至第9天每天暴露于MS 3小时的幼崽在成年大鼠中表现出行为障碍。哺乳期(出生后21天)结束后持续3周口服给予槲皮素和QNP。检测小脑的自闭症样行为、抗氧化参数以及Nrf2、Bax/Bcl-2和Caspase-3的表达。槲皮素(40mg/kg)治疗改善了一些行为障碍。此外,在槲皮素(40mg/kg)治疗的大鼠小脑中观察到氧化应激参数、Nrf2和凋亡因子基因表达的改善(p<0.01)。QNP治疗(10和40mg/kg)显著改善了焦虑样行为、穿越次数和梳理指数(p<0.001)、脂质过氧化(p<0.001),并增加了过氧化氢酶(CAT)(p<0.001)、超氧化物歧化酶(SOD)(p<0.001)、谷胱甘肽过氧化物酶(GPx)(p<0.001)的活性以及谷胱甘肽(GSH)水平(p<0.05)。此外,QNP显著降低了Caspase-3和Bax的表达(p<0.001),但增加了Bcl-2和Nrf2的表达(p<0.001)。这些发现表明,由于QNP具有高生物利用度,其比槲皮素更有效,可减少MS大鼠模型中的自闭症样行为、氧化损伤和凋亡损伤。

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