Jaundice Model

Indication / Application

Preclinical screening of anti-jaundice and choleretic therapeutics, evaluation of hepatoprotective and anti-fibrotic drugs, mechanistic studies on biliary cirrhosis, and safety/efficacy profiling of endobiliary medical devices (such as biliary stents).

Modeling Method

1. Surgical Obstructive Jaundice Platform (Bile Duct Ligation - BDL):

• Under high-magnification microsurgery, the common bile duct of the animal is isolated, doubly ligated with surgical silk, and transected between the ligatures. This causes complete biliary obstruction, leading to stable, highly reproducible systemic hyperbilirubinemia within days.

2. Chemical Intrahepatic Cholestasis Platform:

• Acute/Chronic Chemical Induction: Administration of alpha-naphthylisothiocyanate (ANIT) or alpha-naphthylisothiocyanate variants via oral gavage to induce acute necrosis of biliary epithelial cells, leading to intrahepatic bile duct obstruction and acute jaundice.

Clinical Relevance

• Pathological Homology: Our BDL and ANIT models precisely replicate the biochemical shifts seen in human clinical jaundice, including the rapid accumulation of total bilirubin (T-Bil), direct bilirubin (D-Bil), and bile acids.

• Translational Remodeling: For advanced pipelines, our surgical models showcase the classic progression from initial acute biliary stasis to ductal proliferation, hepatic inflammation, and eventually biliary fibrosis, making them ideal for evaluating long-term anti-fibrotic or tissue-regenerative interventions.

Key Evaluation Endpoints

In Vivo / Phenotypic Evaluation

• Phenotypic Assessment: Visual monitoring of sclera, mucous membranes, and hairless skin regions for distinct yellow coloration (jaundice score).

• High-Resolution Micro-Ultrasound: Non-invasive imaging tracking common bile duct dilation, gallbladder volume changes, and hepatic parenchymal alterations.

• Urinalysis: Serial tracking of bilirubinuria and changes in urine coloration signatures.

Biochemical Profiling (Serum & Hepatic)

• Bilirubin Kinetics (Gold Standard): Automated biochemical measurement of Total Bilirubin (T-Bil), Direct/Conjugated Bilirubin (D-Bil), and Indirect/Unconjugated Bilirubin (I-Bil).

• Liver Function Diagnostics: Comprehensive tracking of Total Bile Acids (TBA), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Gamma-Glutamyl Transferase (GGT).

Histopathology & Immunohistochemistry (Gold Standard)

• Histomorphological Assessment: Standard H&E and Masson’s Trichrome staining to evaluate bile duct proliferation (ductular reaction), hepatocellular necrosis, inflammatory cell infiltration, and peribiliary collagen deposition.

• Immunohistochemistry (IHC) & Special Staining:

  • Biliary Epithelium Tracking: CK19 (Cytokeratin 19) staining to quantify the extent of bile duct proliferation.

  • Fibrosis & Activation Dynamics: alpha-SMA profiling to track hepatic stellate cell activation.

  • Cholestasis Profiling: Hall’s (bilirubin) stain to visualize intrahepatic bile plugs and pigment accumulation.