丹参酮ⅡA磺酸钠在低氧所致肺动脉高压作用机制的分析

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1、-ThemechanismofSodiumTanshinoneIIASulfonateinthetreatmentofhypoxicpulmonaryhypertensionName:HuangHaileSurpervisor:LiJingABSTRACTBackgroundPulmonaryhypertension(PH)isavasculardiseasecharacterizedbythickeningofpulmonaryvesselwallandpulmonaryvesselremodeling.MostCOPD

2、patientsdevelopChronichypoxicpulmonaryhypertension(CHPH),chroniccorpulmonaleanddiedultimately.PlentyofresearchesshowedthatchangesofintracellularCa2+levelisgreatlyrelatedtothecontractionandproliferationofpulmonaryvascularsmoothmusclecells.Amongfivecalciumchannels,s

3、tore-operatedcalciumchannel(SOCC)ismainlyresponsiblefortheimbalanceofintra-calciuminsmoothmuscelcells.SOCCiscomposedofOraiproteinfamily,anditsactivationisreliedonstromalinteractionmolecule(STIM)whichisacalciumsensoronendoplasmicreticulum.Chronichypoxiacanselective

4、lyupregulatetheexpressionofSTIM1andOrai1protein,thereforetookpartinthediseaseprogressionofpulmonaryhypertension.SodiumtanshinoneIIAsulfonate(STS)isthesulfatedformofSodiumtanshinoneIIAthatistheeffectiveconstituentofSalviamiltiorrhiza.RecentresearchesfoundthatSTShav

5、eprotectiveeffecttowardshypoxicpulmonaryhypertensionwhichincludedecreasingmPAP,alleviatingpulmonaryarterysmoothmusclethickeningandrightventriclehypertrophy,butthemechanismremainsunknown.ObjectiveTheexperimentestablishedthehypoxiccellularmodelofpulmonaryarterysmoot

6、hmusclecells(PASMCs)andanimalmodelofchronichypoxicpulmonaryhypertension(CHPH).ThroughobservingtheexpressionofSTIM1andOrai1,intracellularlevelofCa2+andSOCEofPASMCs,III---万方数据---thehemodynamicchangesofinbothCHPHandtheSTSgroup,furtherdiscussingtheeffectivenessandpote

7、ntialmechanismforSTSintreatingCHPH.MethodThisstudywascomposedofprimarycellcultureandanimalexperiment.(1)Forcellexperiment,westernblotwasusedtodetecttheexpressionlevelofSTIM1andOrai1protein.DynamicdigitalCa2+imagingsystemwasusedtomeasure[Ca2+]iandSOCEbyloadingPASMC

8、swithfura2.Foranimalexperiment,chronichypoxicpulmonaryhypertensionanimalmodelwereraisedinahypoxicchamberwithoxygenconcentrationaround(10.5±0.5)%for21day