Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis

Patients with pulmonary fibrosis are at a higher risk of developing pulmonary hypertension, a complication with poor prognosis. At present, the mechanism of this link is still poorly understood. A major obstacle to progress in this area is the lack of a reliable animal model to replicate PF-PH. This study aimed to establish a stable PF-PH rat model. Rats were fasted overnight prior to intervention. Under sodium pentobarbital anesthesia (45 mg/kg), the trachea was intubated with a PE50 tube inserted to a depth of 3 cm (the distance from the glottis to the tube). Bleomycin (BLM) was administered intratracheally as a single dose (5 mg/kg, dissolved in 0.2 mL of 0.9% NaCl). Following the injection, the rats were immediately rotated to ensure even distribution of the BLM. At 35 days after the BLM injection, the rats exhibited progressive impairment of lung function and increased right ventricular systolic pressure and right ventricular hypertrophy, revealing the pathological characteristics of pulmonary hypertension. We provide a general and reliable method to establish a rat model of PF-PH.