Compound xiebai capsule alleviates pulmonary vascular remodeling in monocrotaline-induced pulmonary arterial hypertension in rats

Purpose: To investigate the effect of compound xiebai capsule (CXC) on pulmonary arterial vascular remodeling in a rat model of monocrotaline-mediated pulmonary arterial hypertension (PAH).Methods: PAH model was established through intraperitoneal injection of MCT (60 mg/kg) to male Sprague-Dawley rats. Thereafter, the rats were grouped and treated with saline (control), nifedipine at a dose of 0.02 g/kg/day (positive control), or different doses of CXC (0.67, 1.00 and 1.32 g/kg/day). The effect of treatments on PAH were determined by measurement of hemodynamic indices and right ventricular hypertrophy index (RVHI). Pathological features and ultrastructure of the lung tissue were examined by H & E staining and transmission electron microscopy (TEM). Immunohistochemistry was employed to determine the expressions of proliferation-associated protein and proliferating cell nuclear antigen (PCNA). Western blotting was applied to assay the expressions of apoptotic pathway proteins.Results: CXC treatment decreased the levels of hemodynamic parameters in PAH rats, alleviated RVHI, improved pulmonary vascular remodeling, decreased vascular wall thickness and area (WT and WA), downregulated the expression of PCNA, and enhanced the expressions of apoptosis-related proteins (cytochrome C, caspase-3, and caspase-9).Conclusion: This is the first study to investigate the effect of CXC on vascular remodeling in PAH. The results indicate that CXC markedly reversed the deleterious changes in PAH-induced rat model. Keywords: Pulmonary arterial hypertension, Pulmonary vascular remodeling, Caspase, Cytochrome C, Apoptosis, Compound xiebai capsule