摘要
目的探讨针刺治疗抑郁症的作用机制。方法将SD大鼠随意分为正常组、模型组、针刺组、氟西汀组,每组8只。大鼠抑郁症模型采用慢性不可预知温和应激的方法制备。针刺组每天造模前针刺“百会”和“印堂”穴,每次10 min,每周6次;氟西汀组每天造模前灌胃氟西汀(10 mg/kg),每日1次。检测大鼠体质量和糖水偏好百分率;采用蛋白质印迹法检测海马核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)的蛋白表达;采用实时荧光定量PCR检测海马促炎细胞因子白细胞介素(IL)-1β与IL-18的基因表达;采用酶联免疫吸附法检测海马IL-1β、IL-18,以及抗炎细胞因子IL-4、IL-10的含量。结果与正常组相比,模型组体质量下降(P<0.05),糖水偏好百分率降低(P<0.01),海马NLRP3、ASC和Caspase-1的蛋白表达升高(P<0.01),海马IL-1β、IL-18的基因表达与含量均升高(P<0.01、P<0.05),海马IL-4、IL-10含量降低(P<0.01、P<0.05)。与模型组相比,针刺组、氟西汀组体质量差异无统计学意义(P>0.05),糖水偏好百分率提高(P<0.05),海马NLRP3、ASC和Caspase-1蛋白表达降低(P<0.01),海马IL-1β基因和IL-18基因表达降低(P<0.01、P<0.05),IL-1β和IL-18含量降低(P<0.01、P<0.05),海马IL-10含量升高(P<0.05),而IL-4的含量变化差异无统计学意义(P>0.05)。针刺组与氟西汀组比较,两组间差异无统计学意义(P>0.05)。结论针刺能够改善慢性应激大鼠抑郁样行为、发挥抗抑郁作用,其机制可能与抑制海马NLRP3炎性小体激活及其介导的炎症反应,减少促炎细胞因子,提高抗炎细胞因子水平有关。
Objective To inquire into the mechanism of acupuncture in the treatment of depression.Methods Sprague-Dawley rats were randomly divided into the normal group,the model group,the acupuncture group,and the fluoxetine group(n=8 rats in each).The depression model was established by using chronic unpredictable mild stress method.The"Baihui"(GV20)and"Yintang"(GV29)acupoints were selected in the acupuncture group.Acupuncture treatment was given before modeling each day,with needle retention for 10 minutes,six times a week.Fluoxetine was given intragastrically before modeling each day(10 mg/kg),once daily.The behavior tests,including the body weight and the sucrose preference test were performed.The hippocampal protein expression levels of NLRP3,ASC,and Caspase-1 were measured by Western blotting.The hippocampal gene expression levels of IL-1βand IL-18 were measured by real-time fluorescent quantitative PCR.The hippocampal contents of IL-1β,IL-18,IL-4,and IL-10 were measured by ELISA.Results Compared with the normal group,the body weight and the percentage of sucrose preference test were decreased in the model group(P<0.05,P<0.01),the hippocampal expression levels of NLRP3,ASC,and Caspase-1 were increased(P<0.01),the hippocampal gene expression of the pro-inflammatory factors IL-1βand IL-18 were increased(P<0.01,P<0.05),and the protein levels of IL-1βand IL-18 in the hippocampus were increased(P<0.01,P<0.05),and the levels of anti-inflammatory factors IL-4 and IL-10 were decreased(P<0.01,P<0.05).Compared with the model group,there was no statistical difference in the body weight in the acupuncture and fluoxetine groups(P>0.05),while the percentage of sucrose preference was increased in both the acupuncture and fluoxetine groups(P<0.05).Compared with the model group,the expression levels of hippocampal NLRP3,ASC,and Caspase-1 were decreased(P<0.01),the gene expression levels of the pro-inflammatory factors IL-1βand IL-18(P<0.01,P<0.05)and the protein levels of IL-1βand IL-18 were reduced(P<0.01,P<0.05),and the content of the anti-inflammatory factor IL-10 in the hippocampus was increased(P<0.05).However,there was no statistical difference in the content of IL-4(P>0.05).In addition,there was no statistical difference between the acupuncture and fluoxetine groups(P>0.05).Conclusion Acupuncture treatment could alleviate depressive behavior and exert antidepressant effects,possibly by inhibiting the NLRP3 inflammasome activity and the related inflammatory response,reducing pro-inflammatory cytokine levels,and increasing anti-inflammatory cytokine levels in the hippocampus.
作者
魏高文
邬继红
王红梅
邵瑞洁
卢峻
图娅
WEI Gaowen;WU Jihong;WANG Hongmei;SHAO Ruijie;LU Jun;TU Ya(School of Acupuncture-Moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029,China;The Second People's Hospital of Lishui,Lishui 323000,China)
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2023年第3期427-434,共8页
Journal of Beijing University of Traditional Chinese Medicine
基金
国家自然科学基金项目(No.81774418No.82174508)。
