香连化滞丸治疗犬湿热泄泻的机制探索OA
Mechanistic exploration of Xianglian Huazhi pills in the treatment of damp-heat diarrhea in dogs
本研究围绕香连化滞丸治疗犬湿热泄泻的潜在机制开展临床试验与多组学整合分析.临床试验选择患犬19只(中药组10只、西药组9只),另设健康对照组.治疗前两组患犬证候总积分具有可比性,治疗后两组患犬证候总积分均显著降低(P<0.05),中药组与西药组差异不显著,但中药组患犬中医证候分项积分降低更为明确;中药组总有效率(100.0%)显著高于(P<0.05)西药组(88.9%).通过网络药理学从12味药中筛得多类活性成分,构建"成分-靶点-通路"网络,核心枢纽涉及AKT1、STAT3、TP53、CASP3、EGFR、MTOR等,富集于PI3K-Akt、TNF、炎症性肠病等通路.收集试验犬粪便样本进行16S rDNA测序,结果显示,患犬发病时肠道厚壁菌门等益生菌数量减少、机会致病菌数量增加;经中药干预后,患犬肠道布劳氏菌属、瘤胃球菌群、地中海杆菌属等厌氧发酵菌数量回升,群落结构趋于健康.非靶向代谢组学分析提示,犬湿热泄泻主要扰动脂质与脂肪酸代谢;中药干预可促进核苷/糖代谢与辅因子合成,提升短链脂肪酸及抗氧化相关小分子丰度,降低氧化应激标志物丰度.Spearman相关性分析显示,发酵益生菌与丁酸/戊酸/己酸、γ-谷氨酰-半胱氨酸、肌肽等呈正相关,与肠球菌属、不动杆菌属等呈负相关.综上,香连化滞丸可能通过"多成分-多靶点-多通路"协同,重塑肠道微生态与代谢网络并维护黏膜屏障,从整体上改善湿热泄泻患犬的临床症状.
This study aimed to investigate the potential mechanisms of Xianglian Huazhi pills for treating canine dampness-heat diarrhea using a clinical trial integrated with multi-omics analyses.Nineteen diseased dogs were enrolled(10 in traditional Chinese medicine group and 9 in western medicine group),with an additional healthy control group.The two treatment groups were comparable at baseline.After treatment,the total syndrome scores decreased significantly in both groups(P<0.05),and the between-group difference was not significant;however,the TCM group showed a more pronounced reduction in the TCM-specific subscore.The overall response rate was significantly higher(P<0.05)in the TCM group(100.0%)than that in the western medicine group(88.9%).Network pharmacology identified multiple active constituents from the 12 herbal components and constructed a"compound-target-pathway"network,highlighting hub nodes such as AKT1,STAT3,TP53,CASP3,EGFR and MTOR,enriched in PI3K-Akt,TNF,inflammatory bowel disease and related pathways.Fecal 16S rDNA sequencing showed that disease was associated with decreases in beneficial taxa(e.g.Firmicutes)and increases in opportunistic pathogens,whereas TCM treatment restored anaerobic fermenters including Blautia,Ruminococcus groups,and Mediterraneibacter,shifting the community toward a healthy profile.Untargeted metabolomics indicated that disease mainly perturbed lipid and fatty-acid metabolism;TCM treatment enhanced nucleotide/carbohydrate metabolism and cofactor biosynthesis,increased short-chain fatty acids and antioxidant-related small molecules,and reduced markers of oxidative stress.Spearman correlation analyses revealed positive associations between fermentative probiotics and SCFAs(butyrate,valerate,caproate)as well as γ-glutamyl-cysteine and carnosine,while Enterococcus and Acinetobacter were negatively correlated.Collectively,the evidence suggests that Xianglian Huazhi pills act via a multi-component,multi-target,multi-pathway strategy to remodel the gut microecology and metabolic networks,suppress inflammation and oxidative stress,maintain mucosal barrier function,and thereby improve the clinical state of dogs with dampness-heat diarrhea.
万天;胡重重;李星瑶;范开
中国农业大学动物医学院,北京 100193中国农业大学动物医学院,北京 100193中国农业大学动物医学院,北京 100193中国农业大学动物医学院,北京 100193
农业科技
香连化滞丸湿热泄泻肠道菌群代谢组学网络药理学
Xianglian Huazhi pillsdamp-heat diarrheagut microbiotametabolomicsnetwork pharmacology
《中兽医医药杂志》 2026 (1)
14-23,封3,11
"十四五"国家重点研发计划项目(2022YFD1801102)
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