藏药二十五味珊瑚丸对阿尔茨海默症小鼠肠道菌群的调节

Regulation of Tibetan Medicine 25 Coral Pills on Intestinal Microflora of Alzheimer’s Disease Mice

目的验证藏药验方二十五味珊瑚丸(25 Coral Pills,CP25)是否可通过肠道菌群的调节治疗阿尔兹海默症(Alzheimer′s Disease,AD)。方法APP/PS1双转基因AD小鼠(transgenic Mice,Mt)和A?;(amyloid-β,Aβ)蛋白诱导的AD小鼠(A?;induced Mice,Mi)各60只,按CP25给药剂量分为3组:CP25-100,CP25-200,CP25-400,剂量分别为100、200、400 mg·kg;体重,灌胃给药8周(每周连续给药5天,间歇2天)。水迷宫法检测小鼠的认知能力,免疫荧光染色检测A?蛋白,16S RNA检测小鼠粪便肠道菌群丰度。结果CP25给药后Mt和Mi小鼠的学习能力得到明显改善,A?斑块无明显减少。口服CP25明显纠正了Mt小鼠紊乱的肠道菌群,其中下调脱乳杆菌属、瘤胃梭菌属和不可培养拟杆菌属,上调硫弧菌属和普雷沃氏菌科。诱导模型Mi小鼠肠道菌群无明显失调现象,CP25给药对部分菌群有上调或下调作用。中高剂量CP25(CP25-200,CP25-400)对肠道菌群的调节强度高于低剂量(CP25-100)。结论CP25口服给药显著改善了AD小鼠的认知能力,肠道菌群的调节是其可能的作用机制。

Objective To verify whether the Tibetan medicine prescription of 25 Coral Pills can treat Alzheimer’s disease through the regulation of intestinal flora.Methods APP/PS1 double transgenic AD mice(Mt, n=60) and A?;protein induced AD mice(Mi, n=60) were divided into three groups according to CP25 dose: CP25-100, CP25-200,CP25-400, at 100, 200, 400 mg·kg;weight, respectively. Intravenous administration was given for 8 weeks(5consecutive days per week, 2 days rest). Morris water maze method was used to detect cognition. Immunofluorescence staining was used to detect A-S protein, and 16S RNA was used to detect fecal and intestinal microflora abundance.Results The learning ability of Mt and Mi mice was significantly improved after CP25 administration, but there was no significant reduction of A? plaques. The oral administration of CP25 significantly corrected the disturbed intestinal flora of MT mice, including down-regulation of Lactobacillus, Ruminiclostridium_9 and Uncultured Bacteroidales bacterium,up-regulation of Desulfovibrio and Prevotellaceae GA6A1 group. There was no obvious disturbance of intestinal flora in model Mi mice, and CP25 could up-regulate or down-regulate some flora. CP25-200 and CP25-400 had higher regulation intensity on intestinal flora than CP25-100. Conclusion The oral administration of CP25 significantly improves the cognitive ability of AD mice, and the regulation of intestinal flora is the possible mechanism.