加味礞石滚痰汤对慢性应激小鼠炎症反应和神经损伤的调节作用  

Regulatory Effect of Modified Mengshi Guntan Decoction on Inflammatory Response and Nerve Injury in Mice with Chronic Stress

作　　者：丁一芸[1] 魏蔚 邢佳[1] 姜思源[1] 王雅璇 王素梅[1] DING Yiyun;WEI Wei;XING Jia;JIANG Siyuan;WANG Yaxuan;WANG Sumei(East Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;Beijing First Hospital of Integrated Traditional Chinese and Western Medicine,Beijing 100020,China)

机构地区：[1]北京中医药大学东方医院,北京100078 [2]北京市第一中西医结合医院,北京100020

出　　处：《世界中医药》2024年第22期3458-3466,共9页World Chinese Medicine

基　　金：国家自然科学基金项目(81273799)——健脾止动汤对TS大鼠皮质-纹状体通路谷氨酸转运体及灭活酶GS干预作用的研究;新教师启动基金项目(2022-JYB-XJSJJ067)。

摘　　要：目的:通过观察慢性不可预知性温和应激(CUMS)小鼠行为学,血清、海马组织中炎症介质水平及海马区小胶质细胞和神经元的变化,探讨加味礞石滚汤(JWMS)对模型小鼠神经免疫系统的影响。方法:采用CUMS方法建立非自杀性自伤(NSSI)小鼠模型,以不同剂量JWMS分组灌胃治疗。行为学评价测定小鼠行为学指标,酶联免疫吸附测定(ELISA)法检测血清、海马组织中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)含量;尼氏染色法观察海马区神经元活性变化;免疫荧光法检测神经元特异性核蛋白(NeuN)及小胶质细胞的激活。结果:应激6周后,CUMS小鼠自主活动度、探索程度和对新环境的好奇度均下降。血清和海马组织中IL-6、TNF-α含量明显升高(P<0.01),IL-10明显降低(P<0.01);海马CA1、CA3区尼氏染色变浅(P<0.01),小胶质细胞激活(P<0.01),神经元减少(P<0.01),海马区神经元损伤明显。JWMS治疗后可以提升抗炎因子IL-10水平,降低炎症介质IL-6、TNF-α含量,同时改善海马神经受损。结论:慢性应激可造成炎症反应和神经免疫损伤,JWMS可以调节炎症反应,具有明显的神经元保护作用。Objective:To explore the effect of modified Mengshi Guntan Decoction(JWMS)on the nervous and immune systems of mice by observing their chronic unpredictable mild stress(CUMS)behaviors,as well as changes in the levels of inflammatory mediators in serum and hippocampus and the levels of microglial cells and neurons in the hippocampus.Methods:A mouse model of non-suicidal self-injury(NSSI)was established by CUMS method and was treated by gavage with different doses of JWMS.Behavioral indexes of mice were determined by behavioral evaluation.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)in serum and hippocampal tissue.The changes in neuronal activity in the hippocampus were observed by Nissl staining.NeuN and microglial cell activation were evaluated by immunofluorescence.Results:After six weeks of stress exposure,the autonomic activity,exploration,and curiosity degree about the new environment of mice with CUMS decreased.The contents of IL-6 and TNF-αin serum and hippocampal tissue were significantly increased(P<0.01),and IL-10 content was significantly decreased(P<0.01).At the same time,Nissl staining in the CA1 and CA3 regions of the hippocampus became shallow(P<0.01),and microglial cells were activated(P<0.01).The number of neurons was decreased(P<0.01).The damage to hippocampal neurons was obvious.After JWMS treatment,the level of anti-inflammatory cytokine IL-10 could be increased,and the content of inflammatory mediators IL-6 and TNF-αcould be reduced.The damage to hippocampal nerves could be alleviated.Conclusion:Chronic stress can cause inflammatory response and neuroimmune damage.JWMS can modulate the inflammatory response and has obvious neuroprotective effects.

关 键 词：慢性不可预知性温和应激 非自杀性自伤 情感障碍 炎症反应 免疫激活 神经元损伤 小胶质细胞 加味礞石滚痰汤 

分 类 号：R285.5[医药卫生—中药学]