liver fibrosis model

Liver Fibrosis Model

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Model Introduction

Liver fibrosis is a critical intermediate stage in the progression of chronic liver diseases. Its core biological mechanism lies in the abnormal activation of hepatic stellate cells (HSCs) and the imbalance of apoptosis. The overactivation of HSCs leads to the massive deposition of collagen fibers and extracellular matrix (ECM), driving the evolution of liver tissue from inflammatory injury to irreversible cirrhosis. Liver fibrosis animal models primarily simulate cholestasis, chemical toxic injury, nutritional imbalances (high-fat/alcohol), and composite factors to induce fibrotic lesions in experimental animals (mostly rats, mice, or rabbits) that resemble human pathological characteristics.

Research Applications

This series of models is widely used in the following research fields:

  1. Pathogenesis Research: Investigating the pathological progression of non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and biliary obstructive cirrhosis.
  2. Drug Development and Screening: Evaluating the efficacy of anti-fibrotic drugs and screening relevant serum biomarkers.
  3. Clinical Pathological Simulation: Simulating the pathological features of human liver fibrosis stages S0–S4, particularly liver injury manifestations related to Hepatitis B virus infection and sclerosing cholangitis.

Key Points of Experimental Design

  1. Cholestasis Models:
    • Bile Duct Ligation (BDL): 8–10 week old mice are selected; double ligation and transection of the common bile duct are performed to ensure complete obstruction.
    • Modified Diet Method: Addition of 0.1% DDC (continuous for 8 weeks) or 0.025% ANIT to induce bile duct epithelial injury.
  2. Chemical Injury Models:
    • CCl₄ Method: Administered via intraperitoneal injection; fibrosis typically appears at week 2 and reaches significant levels by week 8.
    • DMN Method: Characterized by strong hepatotoxicity; significant fibrosis is observed 2 weeks after injection, with the degree stabilizing by week 4.
  3. High-Fat Models:
    • Formula Synthesis Method: 80% basal diet + 10%–15% oils + 1.5% cholesterol + 0.5% bile salts; the modeling period is approximately 6 weeks.
    • Choline-Deficient (CD) Diet Method: Utilizing 60%–80% high-fat choline-deficient diet; fibrosis typically emerges from week 6 onwards.
  4. Alcoholic Models: Primarily based on acute alcohol gavage, which can induce inflammatory responses and mild fibrosis within a short period.
  5. Composite Model: Utilizing Sprague-Dawley (SD) rats weighing approximately 200g, combining ethanol gavage, high-fat diet, high-sugar drinking water, and intraperitoneal CCl₄ injection; the modeling period is 8 weeks.

Key Monitoring Indicators

  1. Behavioral and Physical Observation: Food intake, fur luster, activity levels, and urine color (e.g., dark tea-like urine caused by cholestasis).
  2. Biochemical Indicator Detection:
    • Liver Function: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST).
    • Lipid Levels: Triglycerides (TG), Total cholesterol (TC).
  3. Pathological Evaluation:
    • Staining Methods: HE staining, Sirius Red staining.
    • Histological Features: Hepatocyte swelling, vacuolar degeneration, inflammatory cell infiltration, portal and perisinusoidal fibrosis, and diffuse lipid droplet distribution.
  4. Molecular Level: Upregulated expression of vascular cell adhesion molecule (VCAM), osteopontin, and tumor necrosis factor-alpha (TNF-α).

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