Expression and Function of Fxr in Heart and Lung of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats
|School||Central South University|
|Keywords||PAH Right heart failure FXR eNOS|
Objective:We explored the the Farnesiod X receptor (FXR) epression in lung and heart of Mocrotaline (MCT) induced pulmonary arterial hypertension(PAH) rat models and the potential role in PAH pathogenesis.Methods:(1) Divided70SD rats into2groups:Control group and PAH group(MCT group). Control group was established by intraperitoneal injecting with5ml/kg alcohol saline solution while MCT group was established by intraperitoneal injecting50mg/kg MCT.(2) Confirming the models were constructed successfully:①Right heart catheterization was used to test pulmonary artery pressure (PAP) and right ventricular pressure (RVP) related indicators including pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (MPAP).②Calculating the right ventricular hypertrophy index (RVHI).③Hematoxylin-eosin staining (HE staining), collagen fiber staining (Masson staining), wheat germ agglutinin (WGA) staining were used to evaluate the pulmonary vessels remodeling and right ventricle remodeling.(3) Detection the FXR expression in lung and ventricle tissue:①RT-qPCR was used to test the FXR mRNA expression in lung and ventricle.②Western blot (WB) was used to test the FXR protein expression.③Immunohistochemical (IHC) and immunefluorescence (IF) were used to test the protein expression and localization of FXR in lung and ventricle.(4) RT-qPCR was used to test the mRNA expression of eNOS in lung of MCT-4W group.Results:(1) We established PAH and PAH-right heart failure rats models.(2) FXR showed a rise expression in lung of PAH and right heart failure rats while a fall expression in right ventricle.(3) FXR showed a fall expression in left ventricle of right heart failure rats.(4) eNOS mRNA showed a fall expression in lung of PAH rats.Conclusion:(1) FXR may participate in the pathogenesis of PAH.(2) It is a opposite trend in FXR and eNOS transcription level that indicating FXR may be involving in the pathogenesis of PAH by eNOS pathway.