摘要
目的 探讨刺芒柄花素(FMN)在慢性轻度不可预见性应激(CUMS)老龄大鼠认知行为和炎症中的调节作用。方法约70周龄的SD大鼠分为健康对照组、 CUMS模型组、 CUMS联合10 mg/kg FMN组、 CUMS联合20 mg/kg FMN组和CUMS联合1.8 mg/kg盐酸氟西汀(Flu)组。除健康对照组外,其余各组大鼠以CUMS刺激并根据分组给药,持续28 d。糖水偏好、强制游泳实验和旷场实验观测各组大鼠情绪行为。Y迷宫实验检测大鼠学习、记忆和空间认知。HE染色观察脑海马区病理损伤程度,试剂盒检测5-羟色胺(5-HT)和5-羟吲哚乙酸(5-HIAA)含量,原位末端转移酶标记技术(TUNEL)检测脑组织细胞凋亡,ELISA检测外周血中肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(iNOS)和白细胞介素6(IL-6)含量,Western blot法检测脑组织中B细胞淋巴瘤因子2(Bcl2)、Bcl2相关X蛋白(BAX)、活化的胱天蛋白酶9(cleaved caspase-9)、 cleaved caspase-3、 Toll样受体4(TLR4)、髓样分化因子88(MyD88)和磷酸化的核因子κB p65(p-NF-κB p65)蛋白水平。结果 与CUMS模型组比较,CUMS联合20 mg/kg FMN组和CUMS联合1.8 mg/kg Flu组大鼠糖水消耗、旷场中心区域活动时间、旷场移动路程和游泳活动时间均显著增长;新异臂进入次数显著增多,起始臂进入次数和其他臂进入次数显著减少;脑海马区病理损伤得到改善,5-HT和5-HIAA含量显著增高;凋亡细胞及BAX/Bcl2比值、 cleaved caspase-9、 cleaved caspase-3蛋白水平显著降低;TNF-α、 iNOS和IL-6含量显著降低;TLR4、 MyD88和p-NF-κB p65蛋白水平显著降低。结论 FMN能通过阻断海马组织NF-κB通路抑制炎症因子释放改善CUMS老龄大鼠认知行为能力。
Objective To investigate the effects of formononetin(FMN)on cognitive behavior and inflammation in aging rats with chronic unpredictable mild stress(CUMS).MethodssSD rats aged about 70 weeks were divided into healthy control group,CUMS model group,CUMS combined with 10 mg/kg FMN group,CUMS combined with 20 mg/kg FMN group and CUMS combined with 1.8 mg/kg fluoxetine hydrochloride(Flu)group.Except for healthy control group,other groups were stimulated with CUMS and administered drugs for 28 days.Sugar water preference,forced swimming experiment and open field experiment were used to observe the emotional behavior of rats in each group.HE staining was used to observe the pathological injury degree of brain equine area.The contents of 5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)were detected by the kit.The apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)in the brain tissue.The levels of tumor necrosis factorα(TNF-α),inducible nitric oxide synthase(iNOS)and interleukin 6(IL-6)in peripheral blood were measured by ELISA.Western blot analysis was used to detect Bcl2,Bcl2 associated X protein(BAX),cleaved caspase-9,cleaved caspase-3,Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and phosphorylated nuclear factor kB p65(p-NF-kB p65)in brain tissues.ResultssCompared with CUMS model group,sugar water consumption,open field activity time,open field travel distance and swimming activity time significantly increased in the CUMS combined with 20 mg/kg FMN group and the CUMS combined with 1.8 mg/kg Flu group.The number of new outarm entry increased significantly,while the number of initial arm entry and other arm entry decreased significantly.The pathological damage of brain equine area was alleviated,and the contents of 5-HT and 5-HIAA were significantly increased.The ratio of BAX/Bcl2 and the expression of cleaved caspase-9 and cleaved caspase-3 protein as well as the number of apoptotic cells were significantly decreased.The contents
作者
张春华
胡凌云
解云
文静
陈亚迪
ZHANG Chunhua;HU Lingyun;XIE Yun;WEN Jing;CHEN Yadi(Department of encephalopathy,Zhenjiang Hospital of Traditional Chinese Medicine,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Zhenjiang 212000,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2023年第7期610-616,共7页
Chinese Journal of Cellular and Molecular Immunology
基金
江苏省自然科学基金面上项目(BK20181507)。
