liver fibrosis model

Liver Cirrhosis Model

分类：

Model Introduction

The carbon tetrachloride (CCl₄) liver cirrhosis model is a classic chemically-induced animal model. Its core principle involves the utilization of free radicals generated during CCl₄ metabolism in the liver to cause hepatocyte degeneration, necrosis, and inflammatory reactions. Through repeated and long-term injury, the liver is induced to undergo fibrous tissue repair, eventually forming typical cirrhotic pathological changes. This model can be used for pure cirrhosis research or as a basal model to further induce hepatic encephalopathy (HE), simulating clinical acute liver failure (Type A HE) or portosystemic shunting on the basis of chronic liver disease (Type C HE).

Research Applications

  1. Pathogenesis Research: Investigating the pathophysiological evolution of liver cirrhosis and its complications (e.g., hepatic encephalopathy, portal hypertension).
  2. Drug Screening and Evaluation: Used to evaluate the toxicity and efficacy of anti-fibrotic drugs, hepatoprotective drugs, and medications for treating hepatic encephalopathy.
  3. Clinical Simulation: Simulating processes such as hepatocyte destruction, fibrous septa formation, nodular lesions, and the establishment of portosystemic collateral circulation in human cirrhosis.

Key Points of Experimental Design

CCl₄ modeling parameters vary depending on the research objective:

  1. Rat Liver Cirrhosis Model (Combined with Alcohol Induction)
    • Experimental Animals: Male SD rats, 150-200g.
    • Dosage and Route: 60% CCl₄ in olive oil solution, administered via intraperitoneal injection at a dose of 3 mL/kg.
    • Frequency and Duration: Twice weekly for 8 to 12 weeks.
    • Adjuvant Induction: Supplemented with ethanol in drinking water (10% for the first 2 weeks, 20% for weeks 3-4, and 30% after 4 weeks).
  2. Acute Liver Failure / Type A HE Model (Mice)
    • Experimental Animals: BALB/c nude mice.
    • Dosage and Route: CCl₄ mixed with mineral oil at a 1:4 volume ratio, administered via intraperitoneal injection at a dose of 2.5 mL/kg.
  3. Type C HE Model (Drug Combined with Surgery)
    • Experimental Animals: Male SD rats.
    • Administration Mode: Weekly intragastric gavage of water containing CCl₄; initial dose of 20 μL, with subsequent doses adjusted by body weight, for a total of 6 weeks.
    • Follow-up Intervention: Portal vein ligation is performed after the completion of gavage.

Key Monitoring Indicators

  1. Pathological Indicators:
    • Hepatocyte destruction and chronic inflammatory cell infiltration.
    • Nodular lesions (regenerative nodules) encapsulated by fibrous septa.
    • Bile duct proliferation and biliary fibrosis.
    • Brain tissue pathology (e.g., Alzheimer Type II astrocytosis, mild cerebral edema).
  2. Biochemical Indicators:
    • Elevated concentrations of blood ammonia, brain ammonia, and glutamine.
  3. Physiological and Behavioral Indicators:
    • Status of portosystemic shunting.
    • EEG patterns or evoked potentials (specifically for HE models).
    • Intracranial pressure monitoring.
  4. Model Evaluation Parameters:
    • Success rate and mortality rate (e.g., 24h and 48h survival rates in acute models).
    • Body weight change monitoring (used to adjust dosage).

相关产品