SIRT1 Expression In Hypoxic Pulmonary Vascular Smooth Muscle Cells And The Intervened Effect Of Lycium Barbarum Polysaccharides

Object: To investigate the expressions of silent mating type information regulator 2homolog-1(SIRT1)? Matrix Metalloproteinase-9(MMP-9)and hypoxia inducible factor1?(HIF-1?)in hypoxic pulmonary vascular smooth muscle cells(PVSMCs).Methods: PVSMCs were divided into 10 groups: normal oxygen(200mL/L oxygen)cells,2mg/mL LBP-treated normal oxygen cells,DMSO-treated normal oxygen cells,DMSO-treated hypoxic(100mL/L oxygen)cells,(0.5,1,2)mg/mL LBP-treated hypoxic cells,SIRT1 agonist(resveratrol or SR-1720)-treated hypoxic cells,SIRT1 inhibitor(EX-527)-treated hypoxic cells.After 6,12,24 hours,the mRNA and protein expressions of SIRT1?MMP-9 and HIF-1? were measured by real-time quantitative PCR and Western blotting,respectively.In LBP-treated groups,the expressions of SIRT1?MMP-9 and HIF-1?mRNA and protein were detected in 12 hour after LBP treatment.At last,according to previous groups mentioned above,we can go on with cell scratch and transwell test.Results:1.Under the condition of hypoxia,the expression levels of SIRT1 mRNA and protein in PVSMCs decreased,while MMP-9 and HIF-1? mRNA and protein increased.2.Under hypoxia,SIRT1 expression was raised and MMP-9,HIF-1? were reduced by LBP treatement in a dose-dependent manner.3.Resveratrol,which is the specific agonist of SIRT1,could inhibit the expression of MMP-9.4.Under the condition of hypoxia,the ability of migrating and aggressiving in pulmonary vascular smooth muscle cells were increased.However,the migrate and aggressive wereinhibited while LBP treatement.Conclsion:1.Under the condition of hypoxia,the expression of SIRT1 were reduced in pulmonary vascular smooth muscle cells,whereas,the expressions of MMP-9 and HIF-1? were rasied.Therefore,we presume that the expression of the SIRT1 ? MMP-9 and HIF-1? in pulmonary vascular smooth muscle cells may be played a important role in the occurance and development of Hypoxia-induced pulmonary disease.2.When adding LBP to the hypoxic pulmonary vascular smooth muscle cells,we found that the concentration of Lycium Burbarum polysaccharides could enhance the expression of SIRT1.At the same time,the expression of MMP-9 and HIF-1? were decreased.These results told us that Lycium Burbarum polysaccharides might inhibit the occurance and development of Hypoxia-induced pulmonary disease.Furthermore,this function could come ture through regulating the expressions of SIRT1 and related genes.3.Resveratrol,which is the the agonist of SIRT1,could inhibit the expressions of MMP-9,which told us that the expressions of SIRT1?MMP-9 and HIF-1? have a certain relationship.4.Lycium Burbarum polysaccharides could inhibit the migrate and aggressive of vascular smooth muscle cells in hypoxia,this told us that it could resisit some hypoxic pulmonary vascular remodeling and contracting(such as Hypoxia-induced pulmonary disease).