Study On Liver Injury Of Aerobic Exercise-resistant OJ Mice Based On MiR-34a Regulated Wnt Pathway

Objective: To investigate the effect of aerobic exercise on obstructive jaundice-induced liver injury in mice and the differential expression of miRNA-mediated Wnt pathway-related factors in liver and blood tissues in this study.analysis.Methods: A new model of liver injury induced by obstructive jaundice in the common bile duct was constructed by our group.Sixty male KM mice were randomly divided into 6 groups: sham-operated control group(SA)and sham-operated group(SO),model control group(MA),model group(M),aerobic exercise group(TM),and silybin group(SFJB).In addition to the sham operation group and the sham-operated control group,the model of obstructive jaundice in mice was constructed by suspending the common bile duct to the abdominal wall for 48 hours.The silybin group was administered with silybin for about 3 days after ligation of the common bile duct.It was fixed at 4 to 6 pm every day,and the dose was 0.4 ml/time for a total of 6 weeks.The moderate-intensity aerobic exercise group had a training gradient of 0%,no load-bearing,and a speed of 12 m/min(75%VO2max).The training was fixed for 60 minutes per day for 6 days per week for 6 weeks.At the end of the experiment,the mice were fasted overnight,weighed,and the animals were sacrificed by anesthesia to collectblood and isolate the liver tissue.Serum total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured by blood biochemistry.HE staining was used to compare the pathological changes of liver tissue morphology and structure in mice.Immunohistochemistry was used to detect liver tissue wnt1.,?-catenin,cyclinD1 expression and Ki67 cell count;fluorescence quantitative PCR was used to detect the expression of wnt1,?-catenin and cyclinD1 in blood and liver tissues.Results:(1)HE staining showed that the hepatic cells of the SO group were arranged radially;the mice in the M group had atrophy,hepatic cord rupture,nuclear pyknosis and other interstitial erythrocyte accumulation;SFJB group,TM exercise group had the most effect Good,the hepatic lobules are intact,the hepatic cords are arranged neatly,without deformation and necrosis.(2)The results showed that the contents of TBIL,ALT and AST were the highest in group M,and the lowest in group TM and SFJB(P<0.01).(3)Real-time PCR results showed that compared with M group,the expression levels of wnt1,LRP5,?-catenin,cyclinD1 and HGF mRNA in SFJB group and TM group were significantly increased(P<0.05,P<0.01);miRNA results showed that with M group Compared with the TM group and the SFJB group,the miR-34 a level was significantly down-regulated,which was statistically significant(P<0.05).(4)Immunohistochemical results showed that: wnt1,?-catenin,cyclinD1,HGFwere lowly expressed in SO group,?-catenin and cyclinD1 were negative in SO group;compared with M group,TM group,SFJB group wnt1,? The expression of-catenin,cyclinD1 and HGF increased(P<0.01).Compared with group M,the positive expression rate of Ki67 in TM group and SFJB group was significantly increased(P<0.01).Conclusions: Moderate-intensity aerobic exercise can significantly alleviate liver injury induced by obstructive jaundice in mice,and can promote hepatocyte repair in different degrees.Its anti-injury effect is similar to that of SFJB group.Its mechanism of action may play a key role through miRNA-mediated activation of the Wnt signaling pathway.As a non-invasive early detection method,the expression level of RNA in plasma has a good application prospect for the screening of markers in the development of such diseases.