Objective: To study the effect of
polydatin on the injury of
pulmonary arterial hypertension (PAH) induced by
monocrotaline (MCT). Methods: SD rats were induced to develop PAH injury by a single
subcutaneous injection of MCT (60 mg/kg). From the second day, rats in the administration group were orally given
sildenafil (20 mg/kg) and
polydatin (30 or 60 mg/kg) for 3 weeks. At the end of the experiment,
right ventricular hypertrophy (RVH) index of SD rats was calculated, pathological damage was assessed by HE staining, transcription levels of target genes were detected by RT-PCR and Elisa, and expression levels of Endothelial-to-mesenchymal transition (EndMT) related
proteins were detected by immunohistochemistry (IHC) and immunofluorescence (IF). Finally, molecular docking analysis was used to verify the interaction of
polydatin on the main targets. Results:
Polydatin could significantly restore the body function, reduce MCT-induced PAH injury, reduce serum biochemical indices;
polydatin could effectively inhibit EndMT process by decreasing the expression of
N-cadherin, β-
catenin and
vimentin;
polydatin could down-regulate TAGLN expression and increase PECAM1 expression to reduce pulmonary
vascular remodeling. The interaction between
polydatin and EndMT target was confirmed by molecular docking operation. Conclusion: Pharmacological experiments combined with Combining molecular docking was first used to clarify that
polydatin can reduce the pulmonary endothelial dysfunction and pulmonary
vascular remodeling induced by MCT by inhibiting EndMT. The results of the study provide new ideas for the further treatment of PAH injury.