Investigation Of The Effect And Mechanism Of Lactiplantibacillus Plantarum 1201 On Acute Liver Injury And Colitis

Acute liver injury（ALI）is a life-threatening clinical syndrome with a mortality rate of about 20-40%.The morbidity and mortality of colitis are also increasing year by year.Both diseases seriously endanger people’s health,but there is no particularly effective treatment,so it is imperative to find complementary and alternative drugs for the treatment of diseases.Studies have shown that the molecular process of ALI involves the complex interaction of oxidative stress,apoptosis,autophagy and necrosis,and colitis is also closely related to immune response,intestinal flora,oxidative stress,etc.Lactiplantibacillus plantarum 1201 was isolated from Chinese traditional fermented food（Fuzhou vegetable stalk）.It was found that L.plantarum 1201 had good antioxidant capacity in vitro.Therefore,we constructed animal models to explore the effect and potential mechanism of L.plantarum 1201 on ALI induced by carbon tetrachloride（CCl₄）and colitis induced by dextran sulfate sodium（DSS）.The full text is divided into five chapters.In the first chapter,the introduction described the pathogenesis and harm of ALI and colitis,the research progress,action basis and possible mechanism of probiotics.The second chapter describes the isolation,identification and probiotic properties of L.plantarum 1201,including antioxidation and inhibition of pathogenic bacteria.In this experiment,L.plantarum 1201 was screened from Fuzhou vegetable stem,and then its probiotic characteristics was explored by acid tolerance and bile salt tolerance test and a variety of antioxidant capacity tests.Then,a mouse model of S.typhimurium ATCC 13311 infection was established to observe the inhibitory effect of L.plantarum1201 on S.typhimurium ATCC 13311 infections and to explore the inhibitory effect of1201 on pathogenic bacteria in vivo,and to verify the inhibitory effect of L.plantarum1201 on S.typhimurium ATCC 13311 in vitro.The results showed that L.plantarum1201 had strong acid tolerance and bile salt tolerance and excellent antioxidant properties,and could inhibit S.typhimurium ATCC13311 in vivo and in vitro,including its colonization and growth in vitro.The third chapter explained the effect of L.plantarum 1201 pretreatment on the resistance of male adult C57BL/6N mice to CCl₄-induced ALI and its mechanism.In this paper,a CCl₄-induced ALI mouse model was established to explore the mitigation effect of L.plantarum 1201 pretreatment on ALI.Intestinal flora,intestinal integrity,biomarkers of hepatic function,systemic inflammation,autophagy,and apoptosis signals were detected through 16s r RNA gene sequencing,hematoxylin-eosin staining（H&E staining）,real-time PCR,and so on.L.plantarum 1201 could improve the antioxidant capacity of host,regulate intestinal flora,repair intestinal barrier,inhibit the activation of MAPK/NF-κB pathway,inhibit apoptosis and autophagy pathway,relieve inflammation and liver oxidation,and relieve the symptoms of ALI mice.In the fourth chapter,the effect and mechanism of L.plantarum 1201 on colitis induced by DSS were discussed.In this study,an experimental colitis model was established and detected by q PCR,H&E staining,16S r RNA high throughput sequencing and non-targeted metabolomics.L.plantarum 1201 could restore the balance of intestinal flora and increase the concentration of serumα-T and D-mannose in mice,thus reducing the destruction of intestinal barrier,inhibiting DSS-induced inflammation,activating NF-κB signal pathway,and finally alleviating colitis.In the fifth chapter,the prevention of ALI and relief of colitis by L.plantarum1201 by regulating intestinal flora and body signal pathway was summarized,and the later research was prospected.In conclusion,this study screened a probiotic strain L.plantarum 1201 with good antioxidant properties,and clarified the mechanism of L.plantarum 1201 in preventing ALI and relieving colitis for the first time,providing a feasible idea and theoretical basis for new adjuvant therapy of related diseases.