Zhao En-Long, Diwu Yong-Chang, Zhang Hu, Duan Li-Qi, Han Xin-Yue, Wang Ya-Li, Zhou Yuan
the First Clinical College of Shaanxi University of Chinese Medicine Xianyang 712046, China.
Shaanxi University of Chinese Medicine Xianyang 712046, China.
Zhongguo Zhong Yao Za Zhi. 2023 Sep;48(18):5032-5040. doi: 10.19540/j.cnki.cjcmm.20230419.406.
This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg(-1)·d(-1)), a probiotics group(0.39 g·kg(-1)·d(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg(-1)·d(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg(-1)·d(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg(-1)·d(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg(-1)·d(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.
本研究旨在探讨细辛汤（XXD）对阿尔茨海默病（AD）模型快速老化小鼠易感8（SAMP8）学习记忆能力的可能影响，以及其增强神经保护作用和减轻神经炎症的相关机制。将40只SAMP8随机分为模型组（10 mL·kg⁻¹·d⁻¹）、益生菌组（0.39 g·kg⁻¹·d⁻¹）、XXD颗粒高剂量组（H-XXD，5.07 g·kg⁻¹·d⁻¹）、XXD颗粒中剂量组（M-XXD，2.535 g·kg⁻¹·d⁻¹）和XXD颗粒低剂量组（L-XXD，1.267 5 g·kg⁻¹·d⁻¹）。将8只同年龄、同品系的快速老化小鼠抗性1（SAMR1）分配至对照组（10 mL·kg⁻¹·d⁻¹）。灌胃给药10周后，采用Morris水迷宫测试小鼠治疗后空间学习记忆能力的变化。同时，采用免疫荧光染色检测小鼠海马CA1区晚期糖基化终末产物受体（AGER）、Toll样受体1（TLR1）和Toll样受体2（TLR2）的阳性表达。采用蛋白质免疫印迹法检测小鼠海马中沉默信息调节因子2相关酶1（SIRT1）、AGER、TLR1和TLR2的蛋白表达水平。采用酶联免疫吸附测定（ELISA）法评估小鼠海马中Aβ₁₋₄₂水平以及小鼠血清和海马中核因子κB p65（NF-κB p65）、NOD样受体蛋白3（NLRP3）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平。与模型组相比，XXD显著改善了SAMP8的空间学习记忆能力，增加了海马中神经保护因子的表达，降低了神经炎症因子水平，并抑制了Aβ₁₋₄₂的表达。特别是，H-XXD显著增加了小鼠海马中SIRT1的表达，降低了小鼠血清和海马中NF-κB p65、NLRP3、TNF-α和IL-1β的表达水平，并降低了小鼠海马中AGER、TLR1和TLR2的表达（P<0.05或P<0.01）。XXD可能通过增强神经保护作用和抑制神经炎症来改善AD模型SAMP8的空间学习记忆能力。
