摘要
目的 探讨黄连解毒汤对Tau/APP/PS1转基因阿尔茨海默病(Alzheimer's disease,AD)小鼠神经元损伤的影响及机制。方法 将Tau/APP/PS1转基因AD小鼠随机分成模型组和黄连解毒汤低、中、高剂量组,每组10只。选取10只相同月龄的雄性C57BL/6J小鼠作为对照组。药物干预4周后,ELISA法检测小鼠海马组织炎症因子及AD相关病理标志物可溶性淀粉酶前体蛋白α(soluble amyloid precursor protein α,s APPα)、β-淀粉样蛋白(amyloid β-protein,Aβ)40、Aβ42和磷酸化Tau蛋白(phosphorylated tau protein,p-Tau)的水平,免疫荧光双标法检测海马Nod样受体蛋白3(nod-like receptor protein 3,NLRP3)炎性小体和小胶质细胞特异性标志物离子钙结合衔接分子1(ionized calcium binding adapter molecule 1,Iba1)的表达,Western blot检测小鼠海马NLRP3炎性小体信号通路活化情况。结果 与对照组比较,模型组小鼠海马中NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing CARD,ASC)、含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase,Caspase)-1和Iba1表达明显增加(P<0.05),炎症因子白细胞介素(interleukin,IL)-1β、IL-18、肿瘤坏死因子(tumor necrosis factor,TNF)-α水平上升(P<0.05),Aβ40、Aβ42和p-Tau水平及p-Tau/Tau值均升高(P<0.05),s APPα水平下降(P<0.05)。与模型组比较,不同剂量黄连解毒汤治疗组小鼠海马中s APPα水平上升(P<0.05),Aβ40、Aβ42及Tau蛋白磷酸化水平均明显下降(P<0.05),IL-1β、IL-18、TNF-α水平降低(P<0.05),NLRP3、ASC、Caspase-1和Iba1表达减少(P<0.05)。结论 黄连解毒汤可能通过下调AD小鼠海马NLRP3炎性小体信号通路活性,抑制小胶质细胞活化,降低Aβ、p-Tau等神经元毒性病理产物的水平,从而改善海马神经元损伤。
Objective To investigate the effects and mechanisms of Huanglian Jiedu decoction on neuronal damage in Tau/APP/PS1 transgenic Alzheimer's disease(AD)mice.Methods Tau/APP/PS1 transgenic AD mice were randomly divided into low,medium,and high-dose Huanglian Jiedu decoction intervention and model groups,with 10 mice in each group.10 male C57BL/6J mice of the same age were selected as a blank control group.After 4 weeks of drug intervention,ELISA were used to measure the levels of inflammatory factors and AD-related pathological markers such as soluble amyloid precursor proteinα(sAPPα),amyloidβ-protein(Aβ)40,Aβ42,and phosphorylated tau protein(p-Tau)in the hippocampal tissue of the mice.Immunofluorescence double-labeling was used to assess the expression of nod-like receptor protein 3(NLRP3)inflammasomes and microglial-specific marker ionized calcium binding adapter molecule 1(Iba1).Western blot was used to determine the activation of the NLRP3 inflammasome signaling pathway in the mice hippocampus.Results Compared to the blank control group,the model group of mice showed a significant increase in the expression of NLRP3,ASC,Caspase-1,and Iba1 in the hippocampus(P<0.05).Levels of IL-1β,IL-18,and TNF-αwere significantly elevated(P<0.05),as were the levels of Aβ40,Aβ42,and p-Tau,as well as the p-Tau/Tau ratio(P<0.05),while sAPPαlevel decreased(P<0.05).When compared to the model group,mice in different doses of Huanglian Jiedu decoction intervention groups exhibited significant improvements in sAPPα(P<0.05),while the leveles of Aβ40,Aβ42 and p-Tau,as well as the levels of hippocampal inflammatory factors IL-1β,IL-18,and TNF-αwere significantly reduced(P<0.05).Additionally,the expression of NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,and Iba1 were significantly decreased(P<0.05)in the intervention groups.Conclusion Huanglian Jiedu decoction may improve hippocampal neuronal damage by potentially inhibiting the hippocampal NLRP3 inflammasome signaling pathway,suppressing micro
作者
王俊力
张慧芳
徐鑫梓
王睿
杜雅明
刘欣
陈国华
WANG Junli;ZHANG Huifang;XU Xinzi;WANG Rui;DU Yaming;LIU Xin;CHEN Guohua(Wuhan No.1 Hospital,Wuhan 430022,China;Dongying People’s Hospital,Dongying 257091,China;Hubei University of Chinese Medicine,Wuhan 430065,China)
出处
《中国中医基础医学杂志》
CAS
CSCD
2024年第6期986-991,共6页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金项目(81673914)
湖北省武汉市卫健委青年项目(WZ21Q08)
武汉市科技局知识创新专项(2022020801020527)
武汉市科技局应用基础前沿专项(2020020601012302)。
关键词
黄连解毒汤
阿尔茨海默病
三转基因
炎性小体
小胶质细胞
Huanglian Jiedu decoction
Alzheimer's disease
Three transgenic mice
Inflammasome
Microglia
