Puerarin Induces Mitochondria-Dependent Apoptosis in Hypoxic Human Pulmonary Arterial Smooth Muscle Cells 英文参考文献.docVIP

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Puerarin Induces Mitochondria-Dependent Apoptosis in Hypoxic Human Pulmonary Arterial Smooth Muscle Cells 英文参考文献.doc

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Puerarin Induces Mitochondria-Dependent Apoptosis in Hypoxic Human Pulmonary Arterial Smooth Muscle Cells 英文参考文献

PuerarinInducesMitochondria-DependentApoptosisin HypoxicHumanPulmonaryArterialSmoothMuscleCells ChanChen1,ChunChen2,ZhiyiWang3,LiangxingWang2*,LeheYang2,MinjiaoDing2,ChengDing2, YuSun2,QuanLin2,XiaoyingHuang2,XiaohongDu1,XiaoweiZhao1,ChuangyiWang1 1DepartmentofGeriatricMedicine,TheFirstAffiliatedHospitalofWenzhouMedicalCollege,Wenzhou,Zhejiang,China,2DepartmentofRespiratoryMedicine,TheFirst AffiliatedHospitalofWenzhouMedicalCollege,Wenzhou,Zhejiang,China,3DepartmentofEmergencyMedicine,TheSecondAffiliatedHospitalofWenzhouMedical College,Wenzhou,Zhejiang,China Abstract Background:Pulmonaryvascularmedialhypertrophyinhypoxicpulmonaryarterialhypertension(PAH)iscausedinpartby decreasedapoptosisinpulmonaryarterysmoothmusclecells(PASMCs).Puerarin,anisoflavonepurifiedfromtheChinese medicinalherbkudzu,ameliorateschronichypoxicPAHinanimalmodels.Hereweinvestigatedtheeffectsofpuerarinon apoptosisofhypoxichumanPASMCs(HPASMCs),andtodeterminethepossibleunderlyingmechanisms. Methodology/Principal Findings: HPASMCswereculturedfor24hinnormoxiaorhypoxia(5%O2)conditionswithand withoutpuerarin.Cellnumberandviabilityweredeterminedwithahemacytometeroracellcountingkit.Apoptosiswas detectedwithaTUNELtest,rhodamine-123(R-123)fluorescence,acolorimetricassay,westernblots,immunohistochemical staining and RT-PCR. Hypoxia inhibited mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after puerarin (50mM or more) intervention, cell growth was inhibited and apoptosis was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by reduced mitochondrial membrane potential, cytochrome c release fromthemitochondria,caspase-9activation,andBcl-2down-regulationwithconcurrentBaxup-regulation. Conclusions/Significance: Puerarin promoted apoptosis in hypoxic HPASMCs by acting on the mitochondria-dependent pathway.Theseresultssuggestanewmechanismofpuerarinrelevanttothemanagementofclinicalhypoxicpulmonary hypertension. Citation:ChenC,ChenC,WangZ,WangL,YangL,etal.(2012)Puer