• Modeling Mechanism：

  Fulvine (a pyrrolizidine alkaloid from the genus *Pyrrolizidine*) is metabolized in the liver through dehydrogenation to produce active pyrrole derivatives, which are then transported to lung tissue via the bloodstream. These derivatives directly damage pulmonary vascular endothelial cells and smooth muscle: ① Inducing fibrinoid necrosis in pulmonary arteries/microarteries, triggering an inflammatory response primarily characterized by neutrophil infiltration; ② Stimulating the transformation of adventitia fibroblasts into smooth muscle cells, leading to full-thickness thickening of the vessel wall; ③ Simultaneously damaging pulmonary veins/microvenules, resulting in collagen deposition in the venous wall and luminal occlusion, ultimately leading to diffuse pulmonary vascular inflammation and fibrosis.

• Related Products：

  Fulvine (T40688)

• Modeling Method：

  Experimental Subject：

  Rats, Wistar (albino), Female, 6–7 weeks old, Body weight 140–170 g

  Dosage and Administration Route：

  ① Core modelling: Oral (80 mg/kg) or intraperitoneal injection (50 mg/kg), Dissolved in sterile physiological saline (intraperitoneal injection) or suspended in feed (oral), Continuous observation for 4–6 weeks post-administration;
  ② Control treatment: Control group administered equal volume saline solution (intraperitoneal injection) or blank feed (oral administration), with all other conditions identical;

  Dosing Frequency and Duration Model：

  Single Dose

• Validation：

  1. Pathological Indicators: - Vascular Lesions: HE staining showed fibrinoid necrosis in the pulmonary arteries/microarteries (positive in 32/41 rats), neutrophil infiltration in the vessel walls, and abnormal proliferation of smooth muscle cells in the adventitia; thickening of the walls of pulmonary veins/microvenules and collagen deposition (elastic fiber staining showed elastic membrane folds); - Tissue Damage: Diffuse edema and hemorrhage in the lung tissue, interstitial iron pigment deposition (Perl staining positive), and peribronchial lymphocyte aggregation; 2. Cellular Indicators: - Mast Cell Count: The number of mast cells in the lung tissue was significantly increased, reaching 323 cells/mm² after 4 weeks (0.8 cells/mm² in the control group, p<0.01); 3. Functional Indicators: - Right Ventricular Function: The ratio of left ventricular (including interventricular septum) to right ventricular weight decreased to 1-2.5 (3.03-4.55 in the control group), indicating right ventricular hypertrophy.

*Precautions： These animals were euthanized with ether at varying intervals within one to six weeks after using Fuliven. Four rats were euthanized after one week, three after two weeks, four after three weeks, ten after four weeks, ten after five weeks, and another rat was euthanized after six weeks.

*References：Wagenvoort CA,et,al. Effect of fulvine on pulmonary arteries and veins of the rat. Thorax. 1974 Sep;29(5):522-9.