松茸提取物改善AD模型小鼠认知障碍与作用机制

Tricholoma Matsutake Extract Improves Cognitive Impairment in AD Model Mice and Its Mechanism

摘要:

该文为了研究松茸提取物（TM）对阿尔兹海默病（Alzheimer’s disease，AD）模型小鼠的保护机制，利用脑注射Aβ42寡聚体诱导建立AD小鼠模型，评估行为学、神经炎症、氧化应激与肠道菌群相关指标。结果显示，松茸提取物显著改善了AD小鼠的行为与认知障碍。AD病理标志物炎症因子TNF-α、IL-1β及氧化应激标志物MDA的水平在模型组显著升高，但这些变化通过抗炎因子IL-10及抗氧化酶SOD和GSH的上调得以逆转。与模型组相比，TNF-α和IL-1β的表达量分别显著减少了53.98%和53.41%;抗氧化酶SOD和GSH的水平则分别显著上升了88.46%和40.24%。小胶质细胞IBA-1与星形胶质细胞GFAP的表达量显著降低61.39%、55.82%。肠道菌群分析显示，TM能够有效恢复AD小鼠的肠道菌群失调，显著增加产短链脂肪酸（SCFA）菌属的相对丰度，而与炎症相关的菌属相对丰度则显著减少。Firmicutes/Bacteroidetes比值回调进一步表明肠道微生物失衡得以改善。综上所述，松茸提取物能够有效改善神经炎症与氧化应激，恢复肠道菌群失调，发挥改善AD小鼠认知障碍功能，在抗AD方面显示出巨大潜力。

Abstract:

To investigate the protective mechanism of Tricholoma Matsutake extract (TM) on AD mice, an AD mouse model was established using brain injection of Aβ42 oligomers, and behavioral, neuroinflammatory, oxidative stress, and gut microbiota-related indicators were assessed. The findings demonstrated that 2g/kg TM significantly improved behavior and cognitive impairment. Pathological markers of AD, including inflammatory factors TNF-α, IL-1β, and MDA, were elevated in the model mice. However, these changes were reversed by the upregulation of the anti-inflammatory factor IL-10 and the antioxidant enzymes SOD and GSH. Compared to the model group, the expression levels of inflammatory factors TNF-α and IL-1β were significantly reduced by 53.98% and 53.41%, while the levels of antioxidant enzymes SOD and GSH increased significantly by 88.46% and 40.24%, respectively. Additionally, TM inhibited the activation of microglial cell marker IBA-1 and astrocyte marker GFAP, with expression levels significantly decreased by 61.39% and 55.82%. These results indicate that TM improves neural damage by reducing neuroinflammation and oxidative stress.16S rRNA sequencing results indicated that TM effectively restores dysbiosis in AD mice, significantly increasing the relative abundance of SCFA-producing genera such as Lachnospiraceae, Lactobacillus, and Prevotellaceae, while significantly decreasing the abundance of the inflammation-related Proteobacteria. The adjustment of the Firmicutes/Bacteroidetes (F/B) ratio further suggests that the imbalance of gut microbiota has been ameliorated. In summary, TM was found to effectively improve neuroinflammation, reduce oxidative stress, and restore gut microbiota dysbiosis, which collectively enhanced cognitive function in AD mice. Based on these findings, TM shows great potential in the treatment of AD.