酸枣仁-合欢花药对在抑郁症模型大鼠的治疗作用  

Therapeutic Effect of Ziziphi Spinosae Semen-Albiziae Flos on Depression in Rats

作　　者：武尚志 施学丽[1] 张亚光 祁祥 李玲[1] WU Shangzhi;SHI Xueli;ZHANG Yaguang;QI Xiang;LI Ling(Guangxi University of Chinese Medicine,Nanning 530200,China)

机构地区：[1]广西中医药大学,南宁530200

出　　处：《中国实验方剂学杂志》2023年第24期87-94,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广西自然科学基金项目(2020GXNSFAA297179)。

摘　　要：目的:研究酸枣仁-合欢花药对对慢性温和不可预知性应激(CUMS)抑郁模型大鼠海马组织中核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)/趋化因子配体1(CXCL1)/趋化因子受体2(CXCR2)通路的影响。方法:120只雄性SD大鼠随机分为正常组、CUMS组、CUMS+酸枣仁-合欢花低、中、高剂量组(4、8、16 g·kg^(-1))、CUMS+盐酸文拉法辛组(0.008 g·kg^(-1)),每组20只。采用孤养结合CUMS来复制抑郁模型,通过糖水消耗实验、悬尾试验、强迫游泳实验及Morris水迷宫实验测定大鼠行为学和空间学习记忆能力;采用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测大鼠海马组织中NLRP1/CXCL1/CXCR2通路相关因子的变化情况;酶联免疫吸附测定法(ELISA)检测大鼠海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-18、IL-1β及IL-6的含量;组织免疫荧光检测海马组织中活性氧(ROS)水平。结果:与正常组比较,CUMS各处理组大鼠的糖水偏爱度和穿台次数显著降低(P<0.01),而悬尾不动时间、强迫游泳漂浮时间和逃避潜伏期则显著升高(P<0.01);与CUMS组比较,酸枣仁-合欢花各剂量组和盐酸文拉法辛组则明显改变CUMS对上述大鼠行为学和空间学习记忆能力的影响(P<0.05,P<0.01)。与正常组比较,CUMS组大鼠海马组织中NLRP1、CXCL1和CXCR2的蛋白水平均有显著升高(P<0.01),炎性因子IL-18、IL-1β、TNF-α和IL-6的含量显著升高(P<0.01)。与模型组比较,酸枣仁-合欢花和盐酸文拉法辛组明显降低CUMS大鼠海马中NLRP1/CXCL1/CXCR2信号通路的活化及炎症因子的水平(P<0.05,P<0.01),此外,酸枣仁-合欢花药对明显降低CUMS大鼠海马组织中的ROS水平(P<0.05,P<0.01)。结论:酸枣仁-合欢花药对能够改善CUMS抑郁模型大鼠的抑郁行为,其作用机制可能与其抑制ROS/NLRP1/CXCL1/CXCR2信号通路的活化有关。Objective:To investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain,NOD-like receptor thermal protein domain associated protein 1(NLRP1)/chemokine ligand 1(CXCL1)/chemokine receptor 2(CXCR2)pathway in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression.Method:A total of 120 male SD rats were randomized into blank,CUMS,CUMS+low-,medium-,and high-dose(4,8,16 g·kg^(-1))Ziziphi Spinosae Semen-Albiziae Flos,and CUMS+venlafaxine hydrochloride(0.008 g·kg^(-1))groups,with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test,tail suspension test,forced swimming test,and Morris water maze test.Quantitative real-time PCR(Real-time PCR)and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-18,IL-1β,and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species(ROS)in the hippocampus.Result:Compared with the blank group,the CUMS group showed decreased preference to sugar water and times of crossing the platform(P<0.01),and increased immobility time of tail suspension,forced swimming floating time,and escape latency(P<0.01).Compared with the CUMS group,the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats(P<0.05,P<0.01).Compared with the blank group,the CUMS group showed upregulated protein levels of NLRP1,CXCL1,and CXCR2(P<0.01)and elevated levels of IL-18,IL-1β,TNF-α,and IL-6(P<0.01)in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and ve

关 键 词：酸枣仁-合欢花 抑郁症 核苷酸结合寡聚化结构域样受体蛋白1 趋化因子配体1 趋化因子受体2 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R289R33