Mechanism Of Fatty Acid Synthase Inhibitors In Improving Mitochondrial Damage Of Pulmonary Arterial Hypertension

Objective The essay aims to explore the mechanism of fatty acid synthase inhibitors in improving mitochondrial damage of pulmonary arterial hypertension and to search for potential metabolic target of pulmonary arterial hypertension,which will provide some clues for its diagnosis and treatment.Method The model of pulmonary arterial hypertension was established with monocrotaline(monocrotaline,MCT).Fifteen C57bl6 mice(eight weeks),were divided into three groups,which were control group(n=5),model group(MCT group,n=5),intervention group(MCT+fatty acid synthase inhibitors group,n=5),fatty acid synthase inhibitors were continuously injected for 5 weeks and the blood,hearts,lungs and other tissues were acquired.(a)The structure of pulmonary small blood vessels and collagen fibers in control group,model group and intervention group were detected by Masson staining;(b)The one-step TUNEL apoptosis assay kit was used to observe the apoptosis of pulmonary artery smooth muscle cells in the control group,model group and intervention group;(c)Western blot analysis was used to detect the expression of fatty acid synthase(FAS)in lung tissues;(d)The expression of Mfn2 was detected by Real-time quantitative Polymerase Chain Reaction(RT-q PCR).Finally,the obtained experimental datas were analyzed by applying Graphad Prism7.0 software.Results 1.The results of masson staining in lung tissue showed that compared with the control group,the amount of collagen fibers in the pulmonary small blood vessels of the model group increased significantly;Compared with the model group,the collagen fibers of the intervention group decreased and the structure of the pulmonary small blood vessels improved.2.Lung tissue TUNEL staining results showed that compared with the control group,the apoptosis of pulmonary artery smooth muscle cells in the model group was decreased;Compared with the model group,the apoptosis of the intervention group was significantly increased.3.The expression of FAS protein was detected by Western blot : compared with the control group,the expression of FAS in the model group was increased(P<0.05).Compared with the model group,the expression of FAS was decreased in intervention group(P<0.05).4.The expression of Mfn2 m RNA was detected by RT-q PCR: compared with the control group,the expression level of Mfn2 m RNA was down-regulated in the model group(P<0.05).Compared with the model group,the expression of Mfn2 m RNA was up-regulated in the intervention group(P<0.05).Conclusion 1.Fatty acid synthase inhibitors can inhibit the expression of FAS in pulmonary arterial hypertension,improve pulmonary vascular structure and increase cell apoptosis;2.Fatty acid synthase inhibitors can induce mitochondria-associated apoptosis by up-regulating the expression of mitochondrial fusion protein Mfn2 and improve mitochondrial function.