Liver Cirrhosis Model
Liver Cirrhosis Model
Utilizing long-term administration of hepatotoxins such as carbon tetrachloride (CCl4) or thioacetamide (TAA), our platform accurately replicates the pathological transition from chronic inflammatory tissue injury to irreversible nodular cirrhosis.
Modeling Methodologies
Carbon Tetrachloride (CCl4)-Induced Chronic Cirrhosis Model
Rodents receive chronic administration of CCl4 via established systemic dosing regimens over a sustained period. Repeated metabolic activation of CCl4 induces persistent oxidative stress, hepatocyte necrosis, and steady recruitment of inflammatory cells, driving progressive collagen deposition and classical micronodular cirrhosis.
Thioacetamide (TAA)-Induced Chronic Cirrhosis Model
Animals receive chronic administration of TAA over a defined prolonged period. TAA undergoes hepatic bioactivation, causing continuous centrilobular necrosis, prominent ductular response, and uniform bridging fibrosis, serving as a highly reproducible model for parenchymal architecture remodeling.
Clinical Relevance & Translation
- Histological Homology: Replicates the definitive hallmark of clinical liver cirrhosis—the conversion of normal hepatic lobular architecture into regenerative parenchymal nodules surrounded by dense fibrous septa (pseudolobules).
- Portal Hemodynamic Features: Chronic structural distortion and increased intrahepatic vascular resistance lead to secondary portal hypertension and splenomegaly, mirroring human clinical sequelae.
- Cellular Microenvironment: Effectively captures the active transdifferentiation of quiescent hepatic stellate cells (HSCs) into proliferative, collagen-producing myofibroblasts.
Key Evaluation Endpoints
| Endpoint Domain | Specific Parameters & Assays | Pathological Significance |
|---|---|---|
| In Vivo & Physical Parameters | • Body & Liver Mass Profiling • Spleen Index (Splenomegaly) • Direct/Indirect Portal Venous Pressure |
Monitors systemic toxicity, organ burden, and functional progression of portal hypertension. |
| Serum Biochemistry & Liver Function | • ALT, AST, ALP • Total Bilirubin (TBIL) • Serum Albumin (ALB) & Total Protein |
Quantifies active hepatocyte injury, cholestasis, and hepatic secretory and synthetic reserve. |
| Histopathology & Fibrosis Quantitation | • Architecture & Pseudolobule (H&E) • Quantitative Collagen (Sirius Red / Masson) • Fibrosis Staging (Ishak / Metavir Criteria) |
Provides morphometric measurement of Collagen Volume Fraction (CVF) and rates architectural remodeling. |
| Molecular & Cellular Biomarkers | • α-SMA, Collagen Type I/III, TIMP-1 • TNF-α, IL-1β, IL-6, TGF-β1 • Lipid Peroxidation (MDA & Antioxidant Balance) |
Evaluates HSC transdifferentiation, ECM synthesis, inflammatory cascades, and hepatic oxidative stress. |
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