针刺研究2026，Vol.51Issue(3)：284-293,10.DOI:10.13702/j.1000-0607.20250983
基于SIRT1/Nrf2信号通路探讨麦粒灸改善围绝经期失眠大鼠睡眠的机制
Wheat-grain moxibustion improves sleep in perimenopausal insomnia rats by regulating the SIRT1/Nrf2 signaling pathway
摘要
Abstract
Objective To observe the effect of wheat-grain moxibustion(WGM)at"Guanyuan"(CV4),"Mingmen"(GV4),and bilateral"Xuanzhong"(GB39)on the oxidative stress and pyroptosis,and the activity of the Sirtuin 1(SIRT1)/nuclear factor erythroid-2-related factor 2(Nrf2)signaling pathway in the hypothalamus of perimenopausal insomnia(PI)rats,so as to explore its underlying mechanism in improving PI.Methods Thirty-two female SD rats were randomly divided into four groups:sham,model,WGM,and WGM+EX527(n=8 per group).The PI model was established by bilateral ovariectomy combined with an intraperitoneal injection of 4-Chloro-DL-phenylalanine suspension(350 mg/kg)for 2 consecutive days.Rats in the WGM and WGM+EX527 groups received WGM at CV4,GV4 and GB39,with 6 cones for each acupoint.The rats in the WGM+EX527 group received additional intraperitoneal injection of the SIRT1 inhibitor EX527(10 mg/kg)30 min before each moxibustion session.The interventions were conducted once daily for 14 consecutive days.The sleep latency and sleep duration were assessed using the pentobarbital sodium-induced sleep test(righting reflex),and the spontaneous activities(total distance moved,center zone dwelling time,and rearing times in 5 min)were measured using the open field test(OFT).The hematoxylin-eosin(H.E.)staining was used to observe morphological changes in the hypothalamic tissue.Western blot was used to detect protein expression levels of SIRT1,Nrf2,Kelch-like ECH-associated protein1(Keap1),heme oxygenase-1(HO-1),superoxide dismutase(SOD),catalase(CAT),NOD-like receptor thermal protein domain associated protein 3(NLRP3),cysteingl aspartate specific protease 1(Caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC),and gasdermin-D(GSDMD)in the hypothalamus.The qPCR was used to measure mRNA expression levels of SIRT1,Nrf2,Keap1,and HO-1 in the hypothalamus.The reactive oxygen species(ROS)assay kit was used to detect ROS level of hypothalamic tissue.The ELISA was used to measure the content of interleukin(IL)-1β and IL-18 in the hypothalamus.Results Compared to the sham group,the model group showed a striking decrease in the total distance traveled,central zone dwelling time and rearing times in the OFT(P<0.01),and significantly shortened sleep duration and prolonged sleep latency(P<0.01).In comparison with the model group and the WGM+EX527 group,the WGM group showed an obvious increase in the total distance traveled,central zone dwelling time and rearing times(P<0.01),and shortened sleep latency,prolonged sleep duration(P<0.01).Additionally,in comparison with the sham group,the model group had a significant down-regulation in the expression levels of hypothalamic SIRT1,Nrf2,Keap1,and HO-1 proteins and mRNAs,and SOD and CAT proteins(P<0.01),and an obvious up-regulation in the expression levels of NLRP3,Caspase-1,ASC,GSDMD proteins,ROS level,and contents of IL-1β and IL-18(P<0.01)in the hypothalamus.In comparison with the model group and the WGM+EX527 group,both the down-regulation and up-regulation of expression levels of the proteins and mRNAs mentioned above,and ROS level and the contents of IL-1β and IL-18 were reversed in the WGM group(P<0.01,P<0.05).H.E.staining showed that in comparison with the sham group,more hypothalamic neurons were wrinkled with unclear cell structures,varying sizes and uneven distribution in the model and WGM+EX527 groups,which was alleviated in the degree of cell injury in the WGM group,for instance clearer cell structure and uniform distribution.Conclusion WGM can improve the sleep and spontaneous activity of PI rats,which may be related to its functions in alleviation of hypothalamic oxidative stress and pyroptosis by regulating the SIRT1/Nrf2 signaling pathway.关键词
围绝经期/失眠/麦粒灸/沉默信息调节因子1/核因子类红细胞2相关因子2/下丘脑Key words
Perimenopause/Insomnia/Wheat-grain moxibustion/SIRT1/Nrf2/Hypothalamus引用本文复制引用
李欣,黄颖,许智迤,管银玲,林丽霞,蔡慧倩,粟胜勇,张熙,王甜,羊璞,郑广玫,黄文静,黄心雨,尹丽莉..基于SIRT1/Nrf2信号通路探讨麦粒灸改善围绝经期失眠大鼠睡眠的机制[J].针刺研究,2026,51(3):284-293,10.基金项目
广西自然科学基金重点项目(No.2023GXNSFDA026052) （No.2023GXNSFDA026052）
广西研究生教育创新计划项目(No.YCSY2025039) （No.YCSY2025039）
