补肾健脾开心散通过TLR4/NF-κB通路改善AD大鼠炎症的机制  

Mechanism of Bushen Jianpi Kaixin SAN ameliorating inflammation through TLR4/NF-κB pathway in AD rats

作　　者：李莹 靳田田 陈逸飞 王莹 毛迎迎 石和元 孔明望 LI Ying;JIN Tian-Tian;CHEN Yi-Fei(College of Basic Medical,Hubei University of Chinese Medicine,Wuhan 430065,Hubei,China)

机构地区：[1]湖北中医药大学基础医学院,湖北武汉430065 [2]武汉东湖学院

出　　处：《中国老年学杂志》2023年第23期5772-5776,共5页Chinese Journal of Gerontology

基　　金：国家重点研发计划“中医药现代化研究”重点专项(2019YFC1708502)。

摘　　要：目的观察补肾健脾开心散对阿尔茨海默病(AD)大鼠学习记忆能力及脑皮质区Toll样受体(TLR)4/核转录因子(NF)-κB通路相关炎症因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β表达的影响,探讨其作用机制。方法60只SD大鼠随机分为空白(Ctrl)组、模型(AD)组、补肾(BS)组(3.6 g/kg补肾方)、健脾(JP)组(4.05 g/kg健脾方)、开心(KX)组(2.34 g/kg开心方)、补肾健脾开心(BSJPKX)组(9.99 g/kg补肾健脾开心散),每组10只。采用D-半乳糖(D-gal)注射制备AD大鼠模型,BS组、JP组、KX组、BSJPKX组分别以相应药物灌胃,Ctrl组、AD组给予等量生理盐水,1次/d。给药4 w后,Morris水迷宫实验检测学习记忆能力,分别用免疫组化法、实时荧光定量-聚合酶链反应(qRT-PCR)检测脑皮质组织TLR4、NF-κB、TNF-α、IL-1β表达。结果与Ctrl组比较,AD组空间学习记忆能力明显下降(P<0.05,P<0.01),TLR4/NF-κB通路被激活,IL-1β、TNF-α表达显著增高(P<0.05,P<0.01);经补肾健脾开心散治疗后,与AD组比较,BSJPKX组空间学习记忆能力显著改善(P<0.05,P<0.01),TLR4/NF-κB通路被抑制,IL-1β、TNF-α表达显著降低(P<0.05,P<0.01)。结论补肾健脾开心散可以保护AD大鼠神经元,其作用机制可能与调控TLR4/NF-κB信号通路减轻神经炎症有关。Objective To observe the effects of Bushen Jianpi Kaixin SAN on the learning and memory ability of Alzheimer′s disease(AD)rats and the expressions of Toll-like receptors(TLR)4/nuclear factor(NF)-κB pathway and related inflammatory cytokines,like tumour necrosis factor(TNF)-αand interleukin(IL)-1βin cerebral cortex,and to explore its mechanism.Methods 60 SD rats were randomly divided into blank(Ctrl)group,model(AD)group,Bushen(BS)group(3.6 g/kg Bushen prescription),Jianpi(JP)group(4.05 g/kg Jianpi prescription),Kaixin(KX)group(2.34 g/kg Kaixin prescription)and Bushen Jianpi Kaixin(BSJPKX)group(9.99 g/kg Bushen Jianpi Kaixin SAN),with 10 rats in each group.AD mouse model was established by intraperitoneal injection of D-gal.The rats in BS group,JP group,KX group and BSJPKX group were gavaged with corresponding drugs once a day.The rats in Ctrl group and AD group were treated with equal amount of normal saline one time per day.After 4 w,the learning and memory ability was tested by Morris water maze.The expressions of TLR4,NF-κB,TNF-αand IL-1βin cortical tissue were tested by immunohistochemistry or real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Results Compared with the Ctrl group,the spatial learning and memory ability in AD group was significantly decreased(P<0.05,P<0.01),TLR4/NF-κB pathway was activated and the expressions of IL-1βand TNF-αwere significantly increased(P<0.05,P<0.01).After treatment with Bushen Jianpi Kaixin SAN,compared with AD group,the spatial learning and memory ability of BSJPKX group was significantly improved(P<0.05,P<0.01),the TLR4/NF-κB pathway was inhibited,and the expressions of IL-1βand TNF-αwere significantly decreased(P<0.05,P<0.01).Conclusions Bushen Jianpi Kaixin SAN could improve the neurons of AD rats,and its mechanism might be related to the activation of the TLR4/NF-κB signal pathway and reduction of neuroinflammation.

关 键 词：补肾健脾开心散 Toll样受体(TLR)4/核转录因子(NF)-κB信号通路 阿尔茨海默病 神经炎症 

分 类 号：R285.5[医药卫生—中药学]