Effect Of Imatinib On Pulmonary Vascular Remodeling In Rats With Pulmonary Hypertension By Inhibiting Warburg Effect

Background pulmonary arterial hypertension(pulmonary arterial hypertension,PAH)is characterized by progressive pulmonary resistance increased,pulmonary artery reconstruction,eventually leads to right heart failure and death.PAH treatment mainly by reducing the pulmonary artery tension to improve pulmonary circulation resistance,to reverse pulmonary artery reconstruction effect is not obvious,so the PAH patients mortality rates remain high.The study found that pulmonary hypertension morbidity associated with Warburg effect,Warburg effect can improve the PAH,platelet-derived growth factor receptor antagonist imatinib can improve PAH,pulmonary vascular remodeling and right heart failure.Objective to explore whether imatinib by inhibiting the Warburg effect to improve monocrotaline(MCT)PAH model of pulmonary vascular remodeling in rats.Methods 200g-250 g SD rats were randomly divided into normal Con,pulmonary hypertension,IM treatment group,DCA treatment group.Pulmonary hypertension,IM treatment group and DCA intraperitoneal injection of treatment group was 1% of monocrotaline solution,measurement for 60 mg/kg,after 14 days,IM group with IM lavage treatment,measurement of 50 mg/kg;DCA group by DCA lavage treatment,measurement of 80 mg/kg,normal and MCT groups with equal volume of double evaporate water to fill the stomach.MCT injection after 28 days,ultrasonic testing related parameters of pulmonary artery hemodynamics and right heart function,29 days,right cardiac catheterization to measure right ventricular systolic blood pressure.After the completion of execution to samples,for HE staining and immunohistochemical lung tissue of lung tissue and western blot detection related proteins.Results(1)Compared with the Con group,the pulmonary arterial flow rate,PAAT,RVOT flow and TAPSE were decreased in the MCT group(P <0.05);RVID,PA/AO,RVSP,RV/(LV+S)were increased(P <0.05).HE staining showed that the vessel wall in MCT group was thickened and there was a phenomenon of vascular remodeling.(2)Western blot and immunohistochemistry showed that the expression of PDGF,PDGFR and P-PDGFR protein in MCT group was significantly higher than that in Con group(P <0.05)(3)Western blot and immunohistochemical results showed that the expression of Glut1,Glut4,MCT4,PDK1,LDH protein in MCT group was higher than that in Con group(P <0.05),while that of PDH group was lower than that of Con group(4)Compared with MCT group,pulmonary arterial flow rate,PAAT,right ventricular tachycardia velocity and TAPSE were increased in IM group and DCA group(P <0.05).RVID,PA/AO RVSP,RV /(LV)were significantly lower than those in MCT group(P <0.05).HE staining showed that the vessel wall in IM group and DCA group was significantly thinned and the phenomenon of vascular remodeling was improved.(5)Western blot and immunohistochemistry were performed on the lung tissue of Con group,MCT group,IM group and DCA group.Compared with MCT group,the expression of Glut1,Glut4,MCT4,LDH and PDK1 protein in IM group and DCA group was decreased and the expression of PDH protein was increased(P <0.05).Conclusion Imatinib improves pulmonary vascular remodeling in rats with pulmonary hypertension by inhibiting Warburg effect...