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电针对足三里穴的刺激通过激活 Nrf2 介导的抗氧化反应改善了自闭症样行为的大鼠。

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses.

机构信息

Department of Children Rehabilitation, Key Laboratory of Rehabilitation Medicine in Henan, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Institute of Health Engineering, Zhengzhou Health Vocational College, Zhengzhou 450100, China.

出版信息

Gene. 2022 Jun 20;828:146440. doi: 10.1016/j.gene.2022.146440. Epub 2022 Mar 23.

Abstract

OBJECTIVE

Emerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism.

METHOD

Pregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28-48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44-48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured.

RESULT

Electroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2.

CONCLUSION

These data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

摘要

目的

新出现的证据表明,针刺在自闭症中发挥神经保护作用。本研究旨在探讨电针对足三里(ST36)的影响自闭症样行为及其潜在机制。

方法

妊娠大鼠在妊娠第 12.5 天给予丙戊酸(VPA)诱导自闭症谱系障碍(ASD)模型。从出生后第 28-48 天开始,幼鼠每天接受电针对 ST36 的治疗。在 PND28 时,将含有小干扰 RNA Nrf2(Ad-siRNA-Nrf2)的腺病毒载体注射到大鼠的前额叶皮质。在 PND44-48 进行行为分析。在 PND48 时,处死动物并收集大脑进行进一步检测。进行尼氏染色以检测神经元活力。随后测量氧化应激的生化标志物。

结果

与 ASD 大鼠相比,电针对 ST36 改善了运动活动、社交行为、空间学习和记忆以及重复性行为。值得注意的是,电针对前额叶皮质组织中的氧化应激标志物有降低作用,核因子红细胞 2 相关因子 2(Nrf2)从细胞质向细胞核易位,并上调 NADP(H)醌氧化还原酶(NQO1)和血红素加氧酶(HO-1)的水平。然而,电针对 ST36 的这些作用在注射 Ad-siRNA-Nrf2 后被消除。

结论

这些数据表明,电针对 ST36 通过 Nrf2 激活和抗氧化反应保护 ASD 大鼠的神经功能。

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