短链脂肪酸对抑郁模型小鼠肠道菌群及海马TLR4/MyD88/NF-κB通路蛋白的影响  

Effects of short-chain fatty acids on gut microbiota and hippocampal TLR4/MyD88/NF-κB pathway proteins in depression model mice

作　　者：韩文娟 郑亚昕 王岚[2] 甄凤亚 张艳 安翠霞[2] Han Wenjuan;Zheng Yaxin;Wang Lan;Zhen Fengya;Zhang Yan;An Cuixia(Department of Psychiatry and Psychology,the Second Hospital of Hebei Medical University,Shijiazhuang 050005,China;Department of Psychiatry,the First Hospital of Hebei Medical University,the Mental Health Center of Hebei Medical University,the Mental Health Institute of Hebei Medical University,Shijiazhuang 050031,China)

机构地区：[1]河北医科大学第二医院精神心理科,石家庄050005 [2]河北医科大学第一医院精神科,河北医科大学精神卫生中心,河北医科大学精神卫生研究所,石家庄050031

出　　处：《中华行为医学与脑科学杂志》2024年第7期583-589,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：河北省自然科学基金(H2022206544);河北省省级科技计划(SG2021189);河北医科大学第一医院星火科研项目成长基金(XH202208);河北省中央引导地方科技发展资金项目(236Z7751G)。

摘　　要：目的探讨短链脂肪酸(short chain fatty acid,SCFAs)是否通过改善抑郁模型小鼠肠道菌群失调及调控TLR4/MyD88/NF-κB炎性通路产生抗抑郁作用。方法60只SPF级6~8周龄C57BL/6J雄性小鼠根据随机数字表法分为对照组、抑郁模型组、SCFAs组,每组20只。抑郁模型组和SCFAs组小鼠采用慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)方法建立抑郁模型,造模共进行8周,并从第6周开始,SCFAs组小鼠给予短链脂肪酸盐混合溶液饮用,模型组小鼠给予0.78%NaCl溶液饮用,直至造模完成。采用糖水偏爱实验(sucrose preference test,SPT)、强迫游泳实验(forced swimming test,FST)检测小鼠抑郁样行为,旷场实验(open field test,OFT)检测小鼠焦虑样行为。使用16S rRNA基因序列分析小鼠的肠道菌群;采用免疫荧光染色和Western blot方法测定海马组织中星形胶质细胞和TLR4/MyD88/NF-κB炎性通路的活化情况。采用SPSS 26.0进行统计分析,3组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果3组小鼠糖水偏爱率、强迫游泳不动时间和旷场中心区活动时间百分比均差异有统计学意义(F=10.554,10.912,12.599,均P<0.05)。抑郁模型组小鼠的糖水偏爱率和旷场中心区活动时间百分比均低于对照组(均P<0.05),强迫游泳不动时间高于对照组(P<0.05)。SCFAs组小鼠糖水偏爱率[(84.7±3.5)%,(75.3±6.0)%]和旷场中心区活动时间百分比[(7.4±1.4)%,(3.2±0.9)%]均高于抑郁模型组(均P<0.05),强迫游泳不动时间短于抑郁模型组[(110.5±21.5)s,(148.0±20.1)s;P<0.05]。3组小鼠肠道菌群的β多样性差异有统计学意义(P=0.001),与抑郁模型组相比,在科水平,SCFAs组理研菌科与拟杆菌科相对丰度增加,梭菌杆相对丰度降低;在属水平,梭菌属和普雷沃氏菌属相对丰度降低,另枝杆菌属相对丰度增加(均P<0.05)。免疫荧光结果显示,3组小鼠GFAP表达水平差异有统计学意义(F=16.565,P=0.004);抑Objective To investigate whether short chain fatty acid(SCFAs)intervention has an antidepressant effect by improving gut microbiota dysregulation and regulating the TLR4/MyD88/NF-κB inflammatory pathway in depression model mice.Methods Totally 60 SPF grade male C57BL/6 J mice aged 6-8 weeks were randomly divided into three groups:control group,depression model group,and SCFAs group,with 20 mice in each group.The mice in depression model group and SCFAs group were given the chronic unpredictable mild stress(CUMS)stimulations for 8 weeks to establish the depression model.From the 6th week,SCFAs group mice were given a mixed solution of short chain fatty acid salts for drinking,until modeling was completed,meanwhile mice in the model group were given 0.78%NaCl solution for drinking.The depression-like behavior was assessed using the sucrose preference test(SPT)and forced swimming test(FST)following modeling,and the open field test(OFT)was employed to evaluate the anxiety-like behavior of mice.16S rRNA gene sequence was used to analyze the gut microbiota of mice.The activation of astrocytes and TLR4/MyD88/NF-κB inflammatory pathway in hippocampus was determined by immunofluorescence staining and Western blot.SPSS 26.0 was used for statistical analysis,one-way ANOVA was used for comparison among the three groups,and LSD-t test was used for further pairwise comparisons.Results There were statistically significant differences in the sugar water preference rate,the immobility time in FST,and the percentage of activity time in OFT among the three groups(F=10.554,10.912,12.599,all P<0.05).The the sugar water preference rate and the percentage of activity time in OFT of the depression model group were both lower than those of the control group(both P<0.05),and the immobility time in FST was higher than that of the control group(P<0.05).The sugar water preference rate in SCFAs group((84.7±3.5)%,(75.3±6.0)%)and the percentage of activity time in OFT((7.4±1.4)%,(3.2±0.9)%)were both higher than those in the depression mod

关 键 词：抑郁 短链脂肪酸 炎性反应 肠道菌群 慢性不可预知温和应激 小鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]