Study On The Mechanism Of Fatty Acid Synthase Inhibitors To Improve Hypoxic Pulmonary Hypertension By Regulating Autophagy And Apoptosis

ObjectiveThis study preliminarily explored the mechanism of fatty acid synthase inhibitors to improve pulmonary arterial hypertension(PAH)by regulating autophagy and apoptosis.MethodsHuman pulmonary artery smooth muscle cells were cultured in vitro.The control group was treated with normal oxygen concentration,the hypoxia group was induced with hypoxia,and the treatment group was treated with C75(FAS inhibitor)on the basis of hypoxia induction,and cell cycle changes were measured by flow cytometry.15 8-week-old C57bl6 mice were selected and fed in the animal center of Chinese academy of sciences between April 2018 and May 2018.The mice were raised in groups(5 mice in each group)and the indoor temperature and humidity are stable.The mice ate and drank independently.Classical hypoxic model was used to induce PAH model.The control group was raised at normal oxygen concentration for 28 days and intraperitoneally injected with 0.1ml PBS once a week.The hypoxic group was subjected to intraperitoneal injection of 0.1ml PBS at 10% oxygen concentration once a week.The treatment group was given intraperitoneal injection of 0.1ml C75 once a week at 10% oxygen concentration.Western Blot was used to measure the expression of apoptosis and autophagy related proteins in lung tissues.ResultsThe cells in the hypoxic group stayed in G1 and G2 phase after the application of FAS inhibitors;Compared with control group,Bax and Casepase-3 expression were decreased,while Bcl-2,LC3 B and PCNA expression were elavated in hypoxic group.And in treatment group,Bax and Casepase-3 expression were elavated,while Bcl-2,LC3 B and PCNA expression were decreased.ConclusionsFAS inhibitors can help cure PAH by inhibiting cell cycle and reducing cell proliferation.FAS inhibitors have therapeutic effects on PAH,which can reduce the proliferation of PAH cells.When FAS is inhibited,PAH cell apoptosis increases and autophagy decreases,indicating that fatty acid inhibitors can influence the autophagy and apoptosis levels of cells in the lung during the process of PAH.