Современные подходы к индуцированию патологии гепатобилиарной системы у лабораторных животных: сравнительный обзор
Comparative Parameters of Hepatobiliary Pathology Induction Methods in Laboratory Animals
Method | Mechanism | Key Pathology | Duration | Reproducibility | Mortality | Technical Complexity | Cost | Translational Relevance | Best Suited For |
CCl4 | Free radical-mediated hepatocyte necrosis | Centrilobular fibrosis, inflammation | 4–12 weeks | High | Moderate–High (30–40%) | Low | Low | Moderate | High-throughput fibrosis screening |
TAA | Oxidative stress, centrilobular necrosis | Severe fibrosis, cirrhosis | 6–24 weeks | High | High | Low | Low | Moderate–High | Advanced fibrosis, cirrhosis |
DMN | DNA alkylation, periportal injury | Cholestatic fibrosis, bile duct proliferation | 4–8 weeks | Moderate | High | Low | Low | Low | Short-term fibrosis (carcinogenesis risk) |
APAP | NAPQI-mediated hepatotoxicity | Acute liver injury, mild fibrosis | Acute–8 weeks | Moderate | Dose-dependent | Low | Low | Moderate | Acute hepatotoxicity |
BDL | Biliary obstruction | Periportal fibrosis, cholestasis, cirrhosis | 3–4 weeks | High | Very high (65% at 4 weeks) | High | Low | High (obstructive diseases) | Cholestatic fibrosis |
p-BDL | Partial biliary obstruction | Progressive cholestatic injury | 1–2 months | Moderate | Lower than BDL | High | Low | High | Longer-term cholestasis studies |
sBDL | Segmental obstruction | Regional fibrosis comparison | 2–4 weeks | Moderate | Moderate | Very high | Low | Moderate | Local vs. systemic fibrosis mechanisms |
HFD | Metabolic stress, lipotoxicity | Steatosis, NASH, fibrosis | 16 weeks–12 months | Moderate | Low | Low | High | Very high | MASLD, metabolic syndrome |
MCD | Nutritional deficiency | Rapid NASH, fibrosis | 4–8 weeks | High | Low | Low | Moderate | Moderate (no obesity) | Rapid NASH screening |
CDHFD | Combined metabolic + nutritional | NASH, fibrosis | 6–24 weeks | High | Low | Low | High | High | Human-relevant NASH fibrosis |
DDC diet | Porphyrin accumulation, biliary obstruction | Biliary fibrosis, ductular reaction | 4–8 weeks | High | Very low (0%) | Low | Moderate | High | Biliary fibrosis, PHT |
Alcohol | Ethanol metabolism, oxidative stress | Steatosis, inflammation, mild fibrosis | 16–24 weeks | Moderate | Low | Moderate | Moderate | Very high | Alcoholic liver disease |
Immunological | Immune-mediated inflammation | Inflammation, fibrosis | 8–12 weeks | Low | Moderate | Low | Low | Moderate | Immune-mediated fibrosis |
Genetic (Mdr2⁻/⁻) | Spontaneous biliary disease | Biliary fibrosis, cholangiopathy | 8–12 weeks (spontaneous) | High | Low | Very high | Very high | High | Mechanistic studies, chronic cholangiopathy |