针刺对慢性应激抑郁大鼠前额叶皮层小胶质细胞活化的影响Effect of acupuncture on microglia activation in prefrontal cortex of chronic stress-induced depression rats
李晓艳;王红梅;赵雅;李晨;卢峻;邬继红;图娅;
LI Xiao-yan;WANG Hong-mei;ZHAO Ya;LI Chen;LU Jun;WU Ji-hong;TU Ya;School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine;
摘要(Abstract):
目的:观察针刺对慢性应激抑郁大鼠前额叶皮层促炎性细胞因子白细胞介素(IL)-1β、IL-6、离子钙接头蛋白1(Iba-1)和髓系细胞触发受体2(TREM2)表达的影响,探讨针刺抗抑郁的可能机制。方法:SD大鼠随机分为正常组、模型组、针刺组、氟西汀组,每组8只。采用6周慢性不可预知温和刺激方法建立抑郁大鼠模型。针刺组于每日造模前1 h针刺"百会""印堂",每日1次,连续6周。氟西汀组于每日造模前1 h给予氟西汀灌胃(10 mg/kg,1 mg/mL),每日1次,连续6周。采用旷场实验检测大鼠行为学;ELISA法检测大鼠前额叶皮层IL-1β、IL-6含量;免疫组化法检测前额叶皮层小胶质细胞标记物Iba-1表达;实时荧光定量PCR法检测大鼠前额叶皮层TREM2基因表达。结果:与正常组相比,模型组大鼠爬行格数和垂直站立次数均明显减少(P<0.05);与模型组相比,针刺组和氟西汀组爬行格数均显著增加(P<0.05),针刺组垂直站立次数明显增加(P<0.05)。与正常组相比,模型组大鼠前额叶皮层IL-1β、IL-6含量,Iba-1阳性细胞表达明显升高(P<0.05),TREM2基因表达显著降低(P<0.05);与模型组相比,针刺组和氟西汀组大鼠前额叶皮层IL-1β、IL-6含量、Iba-1阳性细胞表达均显著降低(P<0.05),TREM2基因表达明显升高(P<0.05)。结论:针刺可能通过抑制前额叶皮层小胶质细胞活化,减少促炎性细胞因子,增强TREM2表达,发挥缓解抑郁症的作用。
Objective To observe the effect of acupuncture on the expression of proinflammatory cytokines interleukin-1β(IL-1β), interleukin-6(IL-6), microglia marker ion calcium adaptor protein(Iba-1) and triggering receptor expressed on myeloid cells 2(TREM2) in the prefrontal cortex of chronic stress-induced depression rats, so as to explore its antidepressant mechanism. Methods Thirty-two SD rats were randomly divided into normal control, model, acupuncture and fluoxetine groups, with 8 rats in each group. The depression model was established by using chronic mild unpredictable stress methods for 6 weeks. Manual acupuncture stimulation was applied to "Baihui"(GV20) and "Yintang"(GV29) for 10 min before modeling for 6 weeks. Fluoxetine(10 mg/kg, 1 mg/mL) was given to rats of the fluoxetine group by gavage before stress stimulation, once every day for 6 weeks. The open field test was used to evaluate the behavioral changes of rats. The contents of IL-1β, IL-6 in the prefrontal cortex were determined by enzyme-linked immunosorbent assay(ELISA). Immunohistochemistry was used to determine the expression of Iba-1 in the prefrontal cortex. The TREM2 gene expression in the prefrontal cortex was determined by real time fluorescent quantitative polymerase chain reaction(RT-PCR). Results After modeling, the crossing numbers and rearing times were significantly decreased in the model group relevant to the control group(P<0.05). After the treatment, the crossing numbers were significantly increased in the acupuncture and fluoxetine groups(P<0.05), while the rearing times in the acupuncture group were significantly increased(P<0.05). Compared with the control group, the contents of IL-1β, IL-6 and the expression of Iba-1 positive cells in the prefrontal cortex were significantly increased in the model group(P<0.05), while the expression of TREM2 gene in the prefrontal cortex was significantly decreased(P<0.05). After the treatment, the increased levels of IL-1β, IL-6 and Iba-1 positive cells and the decreased TREM2 gene expression were considerably reversed in both acupuncture and fluoxetine groups compared with the model group(P<0.05). Conclusion Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in inhibiting the activation of microglia, reducing the expression of proinflammatory cytokines, and increasing TREM2 expression in the prefrontal cortex.
关键词(KeyWords):
针刺;抑郁症;小胶质细胞;炎性细胞因子;髓系细胞触发受体2
Acupuncture;Depression;Microglia;Inflammatory cytokines;TREM2
基金项目(Foundation): 国家自然科学基金资助项目(No.81774418);; 北京中医药大学基本科研业务费项目(No.2020-JYB-ZDGG-061)
作者(Author):
李晓艳;王红梅;赵雅;李晨;卢峻;邬继红;图娅;
LI Xiao-yan;WANG Hong-mei;ZHAO Ya;LI Chen;LU Jun;WU Ji-hong;TU Ya;School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine;
Email:
DOI: 10.13702/j.1000-0607.200886
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- 李晓艳
- 王红梅
- 赵雅
- 李晨
- 卢峻
- 邬继红
- 图娅
LI Xiao-yan- WANG Hong-mei
- ZHAO Ya
- LI Chen
- LU Jun
- WU Ji-hong
- TU Ya
- School of Acupuncture and Moxibustion
- Beijing University of Chinese Medicine
- 李晓艳
- 王红梅
- 赵雅
- 李晨
- 卢峻
- 邬继红
- 图娅
LI Xiao-yan- WANG Hong-mei
- ZHAO Ya
- LI Chen
- LU Jun
- WU Ji-hong
- TU Ya
- School of Acupuncture and Moxibustion
- Beijing University of Chinese Medicine