基于CXCL12/CXCR4生物轴探讨栀子豉汤对焦虑大鼠模型炎症水平及脑内神经递质的影响  

The effects of Zhizichi Decoction on inflammation levels and neurotransmitters in the brain of anxiety disorder rat model based on the CXCL12/CXCR4 biological axis

作　　者：高路 吕瑾 薛姣 赵喜艳 程盼贵 潘飞辰 吕璐 王新 GAO Lu;LYU Jin;XUE Jiao;ZHAO Xiyan;CHENG Pangui;PAN Feichen;LYU Lu;WANG Xin(Department of Traditional Chinese medicine,Shanxi Yuncheng Central Hospital,Yuncheng 044000,Shanxi,China)

机构地区：[1]山西省运城市中心医院中医科,山西运城044000

出　　处：《西部医学》2025年第4期497-504,共8页Medical Journal of West China

基　　金：山西省中医药管理局科研课题(2022ZYYC176)。

摘　　要：目的基于CXCL12/CXCR4生物轴探讨栀子豉汤对焦虑大鼠模型炎症水平及脑内神经递质的影响。方法90只大鼠随机分为对照组(Control组)、慢性束缚应激组(CRS组)、地西泮组(Diazepam组)、栀子豉汤低剂量组(ZZCD-L组)、栀子豉汤高剂量组(ZZCD-H组)和CXCL12/CXCR4通路抑制剂组(AMD3100组),每组15只。利用慢性束缚应激建立大鼠焦虑症模型。Diazepam组、AMD3100组、ZZCD-L组、ZZCD-H组大鼠分别给予地西泮(1 mg/kg)、AMD3100(1 mg/kg)和栀子豉汤(400 mg/kg、800 mg/kg)治疗。束缚14天后,采用高架十字迷宫实验和旷场实验评估大鼠焦虑样行为;ELISA检测大鼠血清炎症因子(IL-1β、IL-6和TNF-α)含量及海马组织中神经递质(5-HT、Glu、GABA)含量和Glu/GABA比值;RT-qPCR检测海马组织中CXCL12、CXCR4 mRNA水平;Western blot检测海马组织中5-HT受体(5-HT1AR、5-HT2AR)、GABA受体(GABAAR、GABABR)、Glu受体(GluA1、GluA2)和CXCL12、CXCR4蛋白水平。结果与Control组相比,CRS组大鼠焦虑样行为明显增加,血清IL-1β、IL-6、TNF-α水平升高,海马组织中5-HT、GABA、5-HT1AR、5-HT2AR、GABAAR、GABABR水平明显降低,海马组织中Glu、Glu/GABA、GluA1、GluA2水平、CXCL12、CXCR4 mRNA和蛋白水平明显升高(P<0.05);而栀子豉汤能够减轻大鼠焦虑样行为,抑制血清炎症因子IL-1β、IL-6、TNF-α水平、海马组织神经递质Glu水平及CXCL12、CXCR4 mRNA和蛋白水平,并提高神经递质5-HT、GABA水平,呈栀子豉汤剂量依赖性(P<0.05);高剂量栀子豉汤与AMD3100的作用效果相似(P>0.05)。结论栀子豉汤能够减轻大鼠焦虑样行为,抑制大鼠炎症水平及海马组织神经递质Glu水平,并提高5-HT、GABA水平,其可能通过抑制CXCL12/CXCR4生物轴发挥调节作用。Objective To explore the effects of Zhizichi Decoction on inflammation levels and neurotransmitters in the brain of anxiety disorder rat model based on the CXCL12/CXCR4 biological axis.Methods Ninety rats were randomly divided into Control group,chronic restraint stress group(CRS group),Diazepam group,low-dose Zhizichi Decoction group(ZZCD-L group),high-dose Zhizichi Decoction group(ZZCD-H group)and CXCL12/CXCR4 pathway inhibitor(AMD3100 group),with fifteen rats in each group.Chronic restraint stress was used to create rats model of anxiety disorder.Diazepam group,AMD3100 group,ZZCD-L group,and ZZCD-H group rats were treated with Diazepam(1 mg/kg),AMD3100(1 mg/kg)and Zhizichi Decoction(400 mg/kg,800 mg/kg),respectively.After 14 days of confinement,the elevated cross maze experiment and open field experiment were used to evaluate anxiety like behavior in rats.ELISA was used to detect inflammatory factors(IL-1β,IL-6 and TNF-α)content in rat serum,neurotransmitters(5-HT,Glu,GABA)content and Glu/GABA ratio in hippocampal tissues.RT-qPCR was used to detect CXCL12 and CXCR4 mRNA levels in hippocampal tissues.Western blot was used to detect 5-HT receptors(5-HT1AR,5-HT2AR),GABA receptors(GABAAR、GABABR),Glu receptors(GluA1,GluA2)and CXCL12,CXCR4 protein levels in hippocampal tissues.Results Compared with Control group,the anxiety like behavior in CRS group rats were significantly increased,IL-1β,IL-6,TNF-αlevels in serum,5-HT,GABA,5-HT1AR,5-HT2AR,GABAAR,GABABR levels in hippocampal tissues were significantly decreased,Glu,Glu/GABA,GluA1 GluA2 levels,CXCL12,CXCR4 mRNA and protein levels were significantly increased(P<0.05);Zhizichi Decoction could alleviate anxiety like behavior in rats and inhibit serum inflammatory factor IL-1β,IL-6,TNF-αlevels,brain neurotransmitter Glu levels,CXCL12,CXCR4 mRNA and protein levels,and increase neurotransmitter 5-HT and GABA levels,And it shows a dose-dependent effect of Zhizichi Decoction(P<0.05).And the effect of Zhizichi Decoction was similar to AMD3100(P>0.05).Conclusion Zhizi

关 键 词：栀子豉汤 CXCL12/CXCR4 焦虑 炎症 神经递质 

分 类 号：R749.72[医药卫生—神经病学与精神病学]