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 a Mouse Model of Alzheimer’s Disease

摘要:

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:

The protective mechanism of Tricholoma matsutake extract (TM) on an Alzheimer’s disease (AD) mouse model was investigated. The AD mouse model was established using brain injections of Aβ42 oligomers. The behavioral, neuroinflammatory, oxidative stress, and gut microbiota-related indicators were assessed. The results showed that 2 g/kg of TM notably 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 anti-inflammatory factor IL-10 and the antioxidant enzymes SOD and GSH. Compared with the model group, the expression levels of inflammatory factors TNF-α and IL-1β were markedly reduced by 53.98% and 53.41%. In contrast, SOD and GSH levels increased substantially by 88.46% and 40.24%, respectively. TM inhibited the activation of microglial cell marker IBA-1 and astrocyte marker GFAP, with expression levels markedly decreased by 61.39% and 55.82%. These results indicate that TM improves neural damage by reducing neuroinflammation and oxidative stress. The 16S rRNA sequencing results showed that TM effectively ameliorates dysbiosis in AD mice, characterized by a notable increase in the relative abundance of SCFA-producing taxa, including members of Lachnospiraceae, Lactobacillus, and Prevotellaceae, while substantially decreasing the abundance of inflammation-related Proteobacteria. The adjustment of the Firmicutes/Bacteroidetes (F/B) ratio further suggests that the dysbiosis of gut microbiota has been ameliorated. In summary, the study demonstrated that TM effectively ameliorates neuroinflammation, reduces oxidative stress, and restores gut microbiota dysbiosis in AD mice, ultimately leading to improved cognitive function. Thus, TM shows promise as a potential treatment for AD.