Role and mechanisms of probiotics in regulating the ROS/JNK signaling pathway in the pathogenesis of Metabolic fatty liver disease
Objective This study was aimed to investigate the impact of probiotics on regulating the ROS/JNK signaling pathway their underlying mechanism of action in the treatment of metabolic associated fatty liver disease.Methods Male C57BL/6 mice were randomly divided into three groups:control,probiotics,and model groups.Serum levels of ALT,AST,TC,and TG were detected.Moreover,the pathological changes of the liver and ileum tissues were observed by hematoxylin and eosin(H&E)staining,and the content of reactive oxygen species(ROS)in liver tissues was determined.In addition,the levels of D-lactic acid and serum and small intestine diamine oxidase were measured to evaluate the effects of probiotics on the intestinal tract of MAFLD mice.Results Mice in the probiotic group were treated with probiotic intervention,compared with model group,mice hepatic lobule structure was complete,hepatic steatosis in cells and inflammatory cells infiltration were relieved.After C57BL/6 mice were fed the MCD diet,the body weight of the model group was significantly lower than that of the control group,showing poor mental state.After 4 weeks of probiotics treatment,the body weight of mice in the probiotics group was higher than that in the model group,and their mental state was better than that in the model group.Biochemical analysis showed that the levels of ALT,AST,TC,TG,D-lac,serum and small intestinal DAO and ROS in liver in the model group were considerably higher than those in the control group.After 4 weeks of probiotics intervention,serum ALT,AST,TC,TG,D-lac,DAO and ROS levels decreased compared with the model group(P＜0.05).Western blot analysis showed that the expression levels of p-JNk,Caspase-3,Bax in the model group were up-regulated,and the expression level of intestinal tight junction protein ZO-1 was down-regulated compared with the control group.After 4 weeks of probiotics intervention,the expression levels of p-JNK,caspase-3,Bax in the probiotics group were down-regulated compared with that in the model group,while the expression level of intestinal tight junction protein ZO-1 was up-regulated compared with that in the model group(P＜0.05).PCR analysis showed that the expression levels of Bax and Caspase-3 in the model group were significantly increased,while the expression levels of Bax and Caspase-3 in the probiotic group were significantly decreased compared with those in the model group(P＜0.05).Immunohistochemistry analysis showed that the expression levels of P-JNk,Caspase-3 and Bax in the liver of mice in the probiotic group were lower than those in the model group(P＜0.05).The pathological results in our investigation showed that the ileum mucosa in the control group was intact,and the intestinal villi were complete and neatly arranged,without any infiltration of inflammatory cells.However,in the model group the ileum mucosal structure was seriously damaged,with loose and disorderly villi arrangement.Importantly,the ileum mucosa in the probiotic group had fewer injuries and the villi were arranged more neatly.Besides,the ileum tissue of the control group had the lowest Chiu's score range(0-1),whereas that of the model group was 3-4,and the one of the probiotic group was 1-2.Conclusion The increased expression of P-JNk,ROS,Caspase-3 and Bax in MAFLD indicates that it is associated with the onset of MAFLD.The use of probiotics can improve the histological and serological indicators of MAFLD.Western blot,PCR and immunohistochemical results confirmed that probiotics can regulate the expression of factors related to ROS/JNK signaling pathway,reduce oxidative stress and inhibit cell apoptosis to achieve the goal of treating MAFLD.
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