茯苓多糖通过调节肠道微生物群减轻环磷酰胺引起的肠道屏障和免疫损伤

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Abstract：ObjectiveToinvestigatetheprotectiveefectsofPoriacocospolysaccaride（PCP）againstcyclophosphamide（CTX）- inducedintestinalmucosalinjuryanditsimpactongutfloraandtheirmetabolitesinmice.MethodsAdultBALB/Cmicewere randomizedintonoralcontrolgroup，CTmodelgroup，gluamine（positivecontrol）goupandlow-，medium-andig dose PCP treatment groups.In all but the normal control group，the mice were subjected to modeling of CTX-induced intestinalmucosalinjurybyintraperitonealCTXinjectionsfor3days，followedbytreatmentwithgavageofnormalsaline glutamine （300mg/kg） orPCPat75，150，or 300mg/kg for7consecutive days. The colonic expressions of tight junction proteins （uidZO-1）edotoinatendelsestialabilitlojurydl cytokine levels （IL-4， IL-22， IL-17A，and IFN- ⋅γ mRNA） were assessed. Gut microbiota， short-chain fatty acids （SCFAs; mainly acetatesand propionates）andcolonicGPR41 expression were analyzedusing16SrRNA sequencing，GC-MS，andWestern bloting，respectively.Fecal microbiota transplantation （FMT）experiment was conducted tovalidatetheoleof gut microbes in

PCP-mediated repair of intestinal injuries. Results Compared with those in the model group，the mice treatedwithPCPshowedsignificantlyincreasedcolonic occludin and ZO-1 expressions， reduced serum endotoxin，D-lactate and DAO levels，and lowered intestinalpermeabilitywithincreasedcolonicexpressions ofIL-4，IL-22，IL-17A，andIFN- γ mRNA.PCPtreatment obviously increased theabundanceofMuribaculaceae， decreasedLactobacillusandBacteroides，increasedthe contentsofacetateandpropionatein the colon，and upregulated colonic GPR41 expression. The resultsof FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinalinjuriesin mice.Conclusion PCPcan protect

againstCTX-induced intestinalmucosal injuryinmice posiblybymodulating gutfloraandSCFAsmetabolismtoenhance intestinal defense capacity. Keywords： Poria cocos polysaccharide; intestinal mucosal injury; gut flora; short-chain faty acids; GPR41

环磷酰胺（CTX）是一种广泛使用的化疗药物，可用于治疗多种癌症和自身免疫性疾病，如直肠癌、肝癌和溃疡性结肠炎。（剩余22353字）