中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (33): 8744-8750.doi: 10.12307/2026.388

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

隔药饼灸改善免疫抑制模型大鼠的认知功能

史林娟1,徐小珊2,翟春涛1,李  玮1,田岳凤1   

  1. 1山西中医药大学第二临床学院,山西省晋中市   030619;2湖南中医药大学针灸推拿与康复学院,湖南省长沙市   410208
  • 收稿日期:2025-08-15 修回日期:2025-10-16 出版日期:2026-11-28 发布日期:2026-06-16
  • 通讯作者: 田岳凤,博士,教授,博士研究生导师,山西中医药大学第二临床学院,山西省晋中市 030619
  • 作者简介:史林娟,女,2000年生,山西省临汾市人,在读硕士,主要从事艾灸防治疾病效应机制研究。
  • 基金资助:
    国家自然科学基金项目(82174504,81674062),项目负责人:田岳凤

Herbal cake-separated moxibustion improves cognitive function in immunosuppressed rats

Shi Linjuan1, Xu Xiaoshan2, Zhai Chuntao1, Li Wei1, Tian Yuefeng1   

  1. 1The Second Clinical College of Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; 2College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
  • Received:2025-08-15 Revised:2025-10-16 Online:2026-11-28 Published:2026-06-16
  • Contact: Tian Yuefeng, PhD, Professor, Doctoral supervisor, The Second Clinical College of Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China
  • About author:Shi Linjuan, MS candidate, The Second Clinical College of Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China
  • Supported by:
    The National Natural Science Foundation of China, Nos. 82174504, 81674062 (to TYF)

摘要:


文题释义:
免疫抑制大鼠:此研究通过腹腔注射环磷酰胺构建免疫抑制大鼠模型,环磷酰胺剂量为30 mg/kg,连续注射3 d。建模成功的大鼠存在明显的免疫功能低下状态,表现为外周血淋巴细胞计数减少,胸腺、脾脏指数显著降低,精神状态差、饮食少、大量脱毛、体质量明显减轻,旷场实验直立次数、穿格次数及运动距离明显减少,血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平均较正常大鼠降低,免疫应答减弱。
核因子κB:是介导免疫抑制大鼠神经炎症的关键核转录因子,在静息状态下,核因子κB会与核因子κB抑制蛋白结合,以非活性形式存在于细胞质中。环磷酰胺代谢产物丙烯醛等直接刺激脑细胞神经元、小胶质细胞线粒体产生活性氧,活性氧可以激活核因子κB抑制蛋白激酶复合物,核因子κB抑制蛋白激酶磷酸化核因子κB抑制蛋白,使其被泛素化并通过蛋白酶体降解,释放核因子κB并促使核转位,启动促炎基因转录。核因子κB入核后直接结合白细胞介素18基因启动子,可以促进白细胞介素18的转录与表达,放大炎症反应。

背景:环磷酰胺等免疫抑制剂会导致机体的免疫功能受损,从而引起认知功能障碍,隔药饼灸与艾条灸能有效调节机体免疫功能,改善认知障碍,但作用机制尚未完全阐明。
目的:探讨不同灸法干预免疫抑制大鼠认知功能障碍可能的作用机制。
方法:40只SD大鼠随机分为空白组、免疫抑制模型组、隔药饼灸组及艾条灸组,每组10只,后3组使用30 mg/kg环磷酰胺腹腔注射构建免疫抑制模型,连续注射3 d。造模完成后,隔药饼灸组与艾条灸组大鼠进行相应干预10 d,干预完成后采用旷场实验评估大鼠认知功能,ELISA检测血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平以及脑组织白细胞介素18水平,苏木精-伊红染色观察脑组织形态学变化,免疫组化法检测脑组织核因子κB表达。
结果与结论:①与空白组相比,模型组大鼠在旷场实验中站立次数、总运动距离、中央区域移动距离和中央区域停留时间均减少(P < 0.01),血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平均显著降低(P < 0.01,P < 0.001,P < 0.001),核因子κB表达显著升高(P < 0.01),脑组织白细胞介素18水平显著升高(P < 0.001),海马区神经元排列紊乱,部分细胞核固缩深染,有淋巴细胞浸润;②与模型组相比,隔药饼灸组大鼠在旷场实验中站立次数、总运动距离、中央区域移动距离和中央区域停留时间均有不同程度升高(P < 0.05),血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平均升高(P < 0.05,P < 0.01,P < 0.01),核因子κB表达显著降低(P < 0.05),脑组织白细胞介素18水平显著降低(P < 0.01),海马神经排列较整齐,淋巴细胞浸润减少,核固缩和空泡化现象较模型组明显减少;③与模型组比较,艾条灸大鼠在旷场实验中总运动距离、中央区域停留时间均升高(P < 0.05),站立次数与中央区域移动距离无显著差异,血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平升高(P < 0.05),脑组织核因子κB表达、白细胞介素18水平无显著差异;④与艾条灸组相比,隔药饼灸组脑组织白细胞介素18水平显著降低(P < 0.05),其余指标无显著性差异。结果表明:隔药饼灸可能通过抑制核因子κB信号通路激活,从而缓解神经炎症,改善免疫抑制大鼠的认知功能,隔药饼灸对免疫抑制的治疗效果优于艾条灸。
https://orcid.org/0009-0001-4282-5874 (史林娟)


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 免疫抑制, 隔药饼灸, 艾条灸, 核因子κB通路, 神经炎症, 认知功能, 环磷酰胺, 白细胞介素, 肿瘤坏死因子

Abstract: BACKGROUND: Immunosuppressants such as cyclophosphamide impair immune function, leading to cognitive impairment. Herbal cake-separated moxibustion and moxa-stick moxibustion effectively modulate immune function and improve cognitive dysfunction; however, their mechanisms of action remain incompletely understood.
OBJECTIVE: To investigate potential mechanisms by which different moxibustion methods influence cognitive impairment in immunosuppressed rats.
METHODS: Forty SD rats were randomly divided into a blank control group, a model group, a cake-separated moxibustion group, and a moxa-stick moxibustion group, with 10 rats in each group. Cyclophosphamide (30 mg/kg) was intraperitoneally injected for 3 consecutive days to induce immunosuppression rat models, in the latter three groups. Following modeling, rats in the cake-separated moxibustion group and moxa-stick moxibustion groups received corresponding interventions for 10 consecutive days. After intervention, cognitive function was assessed using the open field test. Serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α, as well as brain tissue levels of interleukin-18, were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and immunohistochemistry were used to observe morphological changes and detect nuclear factor κB expression in brain tissue, respectively.
RESULTS AND CONCLUSION: (1) Compared with the blank control group, the number of rearings, total travel distance, distance traveled in the central zone, and time spent in the central zone in the open field test were decreased (P < 0.01); serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly decreased (P < 0.01, P < 0.001, P < 0.001, respectively); nuclear factor κB expression and IL-18 levels in brain tissue were significantly increased (P < 0.001); and hippocampal neurons exhibited disorganized alignment, with some nuclei showing deep staining due to nuclear condensation and lymphocytic infiltration in the model group. (2) Compared with the model group, the number of rearings, total travel distance, distance traveled in the central zone, and time spent in the central zone in the open field test were significantly increased (P < 0.05); serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly elevated (P < 0.05, P < 0.01, P < 0.01), while nuclear factor κB expression was significantly reduced (P < 0.05); brain tissue IL-18 levels in brain tissue were significantly decreased (P < 0.01); and hippocampal neuronal alignment was more orderly, lymphocytic infiltration was reduced, and nuclear condensation and vacuolation were markedly less pronounced in the cake-separated moxibustion group. (3) Compared with the model group, total travel distance and time spent in the central zone in the open field test were significantly increased (P < 0.05), with no significant difference in the number of rearings and distance traveled in the central zone; and serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α significantly increased (P < 0.05), while no significant difference in nuclear factor κB and interleukin-18 levels were found in brain tissues in the moxa-stick moxibustion group. (4) Compared with the moxa-stick moxibustion group, interleukin-18 levels in brain tissue significantly reduced (P < 0.05), with no significant differences in other indicators in the cake-separated moxibustion group. These results suggest that herb cake-separated moxibustion may alleviate neuroinflammation by inhibiting nuclear factor-κB signaling pathway activation, thereby improving cognitive function in immunosuppressed rats. The cake-separated moxibustion shows superior therapeutic efficacy for immunosuppression to moxa-stick moxibustion.


Key words: immunosuppression, cake-separated moxibustion, moxa-stick moxibustion, nuclear factor κB pathway, neuroinflammation, cognitive function, cyclophosphamide, interleukin, tumor necrosis factor

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