| Alcoholic liver disease(ALD)is a common clinical liver disease,mainly caused by drinking a lot of alcoholic beverages.Recently,the molecular mechanism of ALD has made a breakthrough,however,the effective therapeutic method has not been establised.Therefore,the ALD becames one of the most important medical subject,and is attracted widely attention.Probiotics can inhibit the growth of Gram-negative bacteria in the gut and protect the barrier dysfunction of intestinal epithelial cells,which block toxin from the gut to the liver.Domestic and foreign researchers began to study probiotics as a new treatment of ALD,in which the effect of Lactobacillus rhamnosus is more significant.Compared to other probiotics,Lactobacillus rhamnosus plays an important role in tolerance of gastrointestinal acidic environment,human and animal intestinal colonization,and regulates of intestinal flora.LGG also improves intestinal barrier dysfunction as well as enhances immunity.However,the mechanisms of Lactobacillus rhamnosus as treatments of ALD and its potential applications have to be explored adequately.Many studies demonstrated that long-term drinking alcohol could increase intestinal permeability,change tight junctions and promote abnormal intestinal flora.This work aims to study the intestinal barrier dysfunction and intestinal toxins in ALD,and explores the molecular mechanism of Lactobacillus rhamnosus for ALD.In this study,the chronic alcohol-fed model mice were established.Our results showed that the liver fat accumulation and liver injury were more severely than that of the experimental group which were treated with LGG.In addition,LGG alleviated the liver fat accumulation and liver injury may through increase the expression levels of intenstinal tight junction protein ZO-1,Claudin-1,and Occludin,and improve intestinal barrier dysfunction by enhancing HIF-mediated ITF,HIF-2a signal pathway.Since probiotic apoptosis and its metabolites have physiological activities,this study the Lactobacillus rhamnosus supernatant(LGGs)were used as an alternative for liver probiotics treatment.Similarly,we found that LGGs lightened the lver fat accumulation and liver injury in acute alcoholic liver injury model which established by intragastric infusion with alcohol.And the LGGs also inhibited the expression levels of tight junction protein ZO-1,Claudin-1,and Occludin,improved intestinal barrier dysfuction through enhancing ITF,Cathelin related antimicrobial peptide(CRAMP)and HIF-la,HIF-2a expression.To further confirm the protective effects of LGGs,the colon cancer cell lines Caco-2 was used as intestinal epithelial barrier model,and our resultes identified that LGGs could protect Caco-2 cells from alcohol damage and improve the epithelial barrier integrity and permeability.To further investigate the mechanisms of alcohol stimulates intestinal tight junction proteins,the chronic alcoholic liver injury mice and Caco-2 cells were used as cell barrier models.The date showed that the miR122a expression levels were reduced by LGGs.In addition,the expression level of alcohol-mediated occludin was mainly regulated by miR122a.LGGs significantly increased anti-apoptotic protein Bcl-2 expression levels in liver tissue,and decreased pro-apoptotic protein Bax expression levels,which attenuated alcohol-induced hepatic apoptosis.LGGs improve chronic alcoholic fatty liver disease by reducing liver cell apoptosis,and thus effectively prevent chronic alcohol-induced liver injury.Here,we used in vivo and in vitro models to investigate the role of Lactobacillus rhamnosus in the prevention and treatment of ALD,and the mechanism was that the LGG enhances the HIF-mediated signal pathway,improves intestinal epithelial barrier integrity and permeability,upregulates miR122a,and inhibits hepatic apoptosis.This research not noly provided an novel mechanism of alcohol and probiotics on bacteria integrity,intestinal microflora balance and endotoxemia,but also supplied theoretical basis and potential for clinical treatments of ALD. |
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