电针对肝郁脾虚型抑郁症大鼠HMGB1/RAGE/TLR4通路及小胶质细胞活化的影响  

Impacts of electroacupuncture on HMGB1/RAGE/TLR4 pathway and microglia activation in rats with liver depression and spleen deficiency type of depression

作　　者：徐欣[1] 高丽丽[1] 李文萍[1] XU Xin;GAO Lili;LI Wenping(The Second People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China)

机构地区：[1]福建中医药大学附属第二人民医院,福建福州350003

出　　处：《陕西中医》2024年第11期1471-1475,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：福建省卫生健康委员会科技计划项目(2023GGA072)。

摘　　要：目的:探究电针对肝郁脾虚型抑郁症大鼠高迁移率族蛋白盒1/晚期糖基化终产物/toll样受体4(HMGB1/RAGE/TLR4)通路及小胶质细胞活化的影响。方法:将大鼠随机分为对照组、模型组、电针组及HMGB1激活剂组,除对照组外均构建肝郁脾虚型抑郁症大鼠模型。观测大鼠体重及行为学表现;采用HE染色法观察大鼠海马组织病理变化;采用免疫组化检测大鼠海马组织中钙接头蛋白1(Iba-1)、一氧化氮合酶(iNOS)的表达情况;采用蛋白免疫印迹(Western blotting)检测海马组织中HMGB1/RAGE/TLR4信号传导通路相关蛋白HMGB1、RAGE、TLR4的表达水平。结果:相较于对照组,模型组大鼠长期动作行为缓慢、脱毛、毛发粗糙、凌乱无光泽,排泄存在水样便,大鼠海马区神经细胞出现明显结构损伤,且大鼠体重及在旷场箱内运动的总路程减少(P<0.05),而在旷箱中央停留时间、休息时间以及海马组织中Iba-1、iNOS、HMGB1、RAGE和TLR4表达升高,差异有统计学意义(均P<0.05)。相较于模型组,电针组大鼠精神状态有所好转,海马区神经细胞损伤程度减轻,细胞形态良好且排列逐渐趋于有序,大鼠体重、在旷场箱内运动总路程提高,差异有统计学意义(均P<0.05)。结论:电针能够抑制肝郁脾虚型抑郁症大鼠小胶质细胞活化,其作用机制可能与抑制HMGB1/RAGE/TLR4通路有关。Objective:To investigate impacts of electroacupuncture on high mobility group protein 1/advanced glycation end products/toll-like receptor 4(HMGB1/RAGE/TLR4)pathway and microglia activation in rats with liver depression and spleen deficiency type of depression.Methods:Rats were stochastically separated into control group,model group,electroacupuncture group and HMGB1 activator group.Except for the control group,all rat models of liver depression and spleen deficiency of depression were constructed.The body weight and behavioral manifestations of rats were observed.HE staining method was used to observe pathological changes in rat hippocampal tissue.Immunohistochemistry was applied to detect expression of ionized calcium bindingadaptor molecule-1(Iba-1)and inducible nitric oxide synthase(iNOS)in rat hippocampal tissue.Western blotting was used to detect expression levels of HMGB1/RAGE/TLR4 signaling pathway related proteins HMGB1,RAGE,and TLR4 in hippocampal tissue.Results:Compared with the control group,long-term movement behavior of the model group rats were slow,with depilation,rough and messy hair,no luster,and watery stools in excretion.There was obvious structural damage to nerve cells in the hippocampus of the rats,and the body weight and total distance traveled during exercise in the open field box are reduced(P<0.05),the central residence time and rest time in open field box,the expression levels of Iba-1,iNOS,HMGB1,RAGE,and TLR4 in the hippocampus tissue increased,difference statistically significant(all P<0.05).Compared with the model group,the mental state of rats in the electroacupuncture group was improved,the damage degree of nerve cells in the hippocampus reduced,the cell morphology was good,arrangement gradually tended to be orderly,and the body mass and total distance of movement in open field of rats increased,difference statistically significant(all P<0.05).Conclusion:Electroacupuncture can inhibit activation of microglia in rats with liver depression and spleen deficiency type of depression.It

关 键 词：抑郁症 肝郁脾虚型 电针 高迁移率族蛋白盒1 晚期糖基化终产物 toll样受体4通路 小胶质细胞 

分 类 号：R749.4[医药卫生—神经病学与精神病学]