Animal Model and Clinical Study of the Mechanism of Aerobic Exercise in Improving Obstructive Jaundice Liver Injury through miR-154 Regulating Wnt Signaling Pathway
PENG Rui1, MAO Haifeng1, ZHANG Xiaolian2, ZHANG Yu1*
This paper explored the mechanism of aerobic exercise intervention in improving the liver fibrosis of patients and mice with obstructive jaundice through miR-154 regulating Wnt signaling pathway. In the animal experiment, 3-week-old male KM mice were used. First, the mouse common bile duct was suspended in the abdominal wall to construct an obstructive jaundice model. After the construction of the model, the mice were randomly divided into the model group (M), the aerobic exercise group (E), and the blank control group (B), 10 mice in each group. In the clinical study, 20 patients with obstructive jaundice were selected and divided into the regular exercise group (RE) and obstructive jaundice group (OJ), 10 cases in each group. The experiment was carried out to evaluate the improvement of liver injury mediated by aerobic exercise through general behavioral assessment, enzyme-linked immunosorbent assay (ELisa), HE staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results indicated that, in 72 h after construction of the model, the urine color of the mice became deepened, the stool was light gray, and there were obvious scratches on the lower back and abdomen. Under the microscope, it could be seen that the hepatic cell cords of the M group became disorderly and the nucleus was deformed or moved to the cell edges, and cells showed vacuolation. In the M group, the serum total bilirubin (TBIL), total bile acid (TBA), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) protein levels were significantly increased (P<0.01). Compared with the M group, the serum liver fibrosis indicators procollagen III N-terminal propeptide (PIIINP), type IV collagen (IV-C), laminin (LN), hyaluronic (HA) content significantly decreased, and Wnt5a, β-catenin, GSK-3β and MMP-9 protein content in liver tissue also decreased (P<0.01). Besides, miR-154, Wnt5a, β-catenin, GSK-3β, MMP-9 mRNA expressions in the blood declined (P<0.01). According to the clinical observation, the sclera, mucous membrane and skin color of OJ group were dark yellow and there were itching symptoms in many parts, the stool showed white clay color, the jaundice symptoms in RE group improved significantly and the contents of PIIINP, IV-C, LN and HA proteins in liver fibrosis decreased (P<0.01). Compared with the RE group, the serum TBIL, TBA, ALT, and AST protein contents in OJ group increased, and miR-154, Wnt5a, β-catenin, GSK-3β, MMP-9 mRNA expressions increased (P<0.01). In conclusion, the aerobic exercise intervention can reduce the expression level of miR-154, accordingly inhibiting the regulation mechanism of Wnt/β-catenin signaling pathway, so the aerobic exercise has anti-fibrosis effect in animal model and clinical application of treatment of obstructive jaundice.
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