摘要
目的研究桃红四物汤(Tao Hong Si Wu decoction,THSWD)多糖与小分子的协同作用。方法采用线栓法构建大鼠脑缺血再灌注模型(middle cerebral artery occlusion/reper-fusion,MCAO/R),灌胃THSWD、THSWD小分子(THSWDX)和THSWDPX(THSWD多糖加小分子)各7天,每天1次。末次给药后取脑、血清、粪便和结肠,TTC染色法检测脑梗死面积;HE染色法检测结肠病理情况;采用16S rRNA高通量测序检测大鼠肠道菌群的变化;全靶向代谢组学检测血清代谢物差异。结果多糖存在的组别中大鼠的脑梗死面积显著缩小(P<0.01),结肠隐窝结构完整,杯状细胞较为丰富,上皮结构较为完整;16S rRNA高通量测序结果显示,与模型组比较,各给药组均可以降低拟杆菌门的丰度,THSWD组的效果尤甚,同时增加变形菌门、厚壁菌门和疣微菌门的丰度,各给药组中的氨基酸含量上升而有机酸含量下降,与THSWD组比较,单独给药的小分子组拟杆菌门的丰度仍然较高,并且缺少丁酸、戊二酸等短链脂肪酸成分,在色氨酸代谢和嘧啶代谢途径上存在差异。结论多糖与小分子存在协同作用,其主要靶点是肠道菌群,具体体现在以下两个方面:①多糖可以改善菌群结构,促进小分子被更好地吸收;②肠道菌群的改变影响了代谢产物的变化,不同的代谢产物通过不同的途径参与疾病的恢复。
Objective The effect of total polysaccharides on the absorption of small molecule components in Taohong Siwu Decoction was studied.Methods A rat middle cerebral artery occlusion/reper-fusion(MCAO/R)model was established by using thread occlusion method.Intragastric administration of THSWD.THSWD small molecule(THSWDX)and THSWDPX(THSWD polysaccharide plus small molecule)was performed once a day for 7days each.Brain,serum,stool and colon were collected after the last dose.TTC staining was used to detect the infarct size,HE staining was used to detect the pathology of colon.16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora in rats.Serum metabolite differences were detected by fully targeted metabolomics.Results In the polysaccharide group,the cerebral infarction size was significantly reduced,the colonic crypt structure was intact,goblet cells were abundant,and the epithelial structure was intact.16S rRNA high-throughput sequencing results showed that compared with the model group,the abundance of Bacteroidetes could be decreased in each administration group,especially in THSWD,and the abundance of Proteobacteria,Firmicutes and verrucobacteria could be increased at the same time.The amino acid content in each administration group increased while the organic acid content decreased,The abundance of Bacteroidetes in the small molecule group administered alone was still high.and the short-chain fatty acid components such as butyric acid and glutaric acid were missing.and there were differences in tryptophan metabolism and pyrimidine metabolism pathway.Conclusion Polysaccharides and small molecules have synergistic effects.and their main targets are intestinal flora,which are embodied in the following two aspects:①Polysaccharide can improve the structure of the flora,and promote better drug absorption;②Changes in the intestinal floraffect the changes of metabolites.and different metabolites participate in body metabolism through different ways to accelerate the recovery of the lesion site.
作者
谢晴晴
张雪婷
王晓群
刘竹青
韩岚
XIE Qingqing;ZHANG Xueting;WANG Xiaoqun(School of Pharmacy,Anhui University of Traditional Chinese Medicine,Auhui 230012,China)
出处
《医学研究杂志》
2025年第9期49-55,35,共8页
Journal of Medical Research
基金
国家自然科学基金资助项目(82074152,82204805,82304912)
安徽省高校自然科学研究重点项目(2023AH050866)。
关键词
多糖
小分子
代谢组学
肠道菌群
Polysaccharide
Small molecules
Metabolomics
Intestinal flora
