简介:Thepanaxnotoginsengsaponin(PNS)hadbeenclinicallyusedforthetreatmentofcardiovasculardiseasesandstrokeinChina.IthadbeendemonstratedthatPNScouldprotectcardiomyocytesfrominjuryinducedbyischemi-a,buttheunderlyingmolecularmechanismsofthisprotectiveeffectwerestillunclear.ThisstudywasaimedtoinvestigatetheprotectiveeffectandmolecularmechanismsofPNSonapoptosisinH9c2cellsinvitroandratmyocardialischemiainjurymodelinvivo.Annexin-V/PIassayshewthatPNScouldprotectH9c2cellsfromapoptosisinducedbyserum,glucoseandoxygendeprivation(SGOD)inadose-dependentmanner.However,theanti-apoptoticeffectofPNSwasreversedbyLY294002,aspecificPI3Kinhibitor.ThisantiapoptoticeffectofPNSwasconfirmedbyJC-1,aspecificprobeofmitochondrialmembranepotentialstaining.PNScouldsignificantlyincreasephos-AktinH9c2cellsbyWesternblotassaysanditseffectcouldbeinhibitedbyLY294002.Furthermore,PNScouldimproveischemic-inducedleftventricularfunctionasreflectedbyEF,LVDdandLVDs.PNScouldalsoinhibitedcellularapoptosisinmyocardialtissuesinischemicratsbyTUNELassay.PNSadministrationalsoincreasedtheexpressionofphos-Aktinratischemicmyocardialtissues.TheseresultssuggestedthatPNScouldprotectmyocardialcellsfromapoptosisinducedbyischemiainvitromodelandinvivomodelthroughactivating-PI3K/AktsignalpathwaywhichmaybemeaningfulforfurtherunderstandingthemolecularmechanismsofcardiacprotectionofPNS.Andtheresultsmightbeusefulintreatmentofmyocardialischemiainfuture.
简介:目的:观察热应激诱导心肌热休克蛋白(HSP)70表达上调,对兔快速心房起搏致房颤心肌钙激活钾通道(KCa)3.1表达的影响。方法:将24只新西兰大白兔随机分为假手术组(n=8,仅植入电极而不起博)、起搏组(n=8,以600次/min快速起搏右心房6h)和热应激起搏组(热应激组,n=8,先行热应激预处理,再行与起搏组一样的快速起搏)。结果:与假手术组和起搏组比较,热应激组心脏各部位HSP70mRNA和蛋白表达显著上调[HSP70蛋白,左房:(39.00±3.21)比(39.75±2.82)比(69.75±3.45),右房:(38.38±2.92)比(39.50±3.89)比(69.00±2.93),左心耳:(37.75±3.28)比(39.00±3.89)比(68.63±3.23),右心耳:(37.00±3.85)比(38.38±3.74)比(68.75±2.82)],P均〈0.01,而起搏组和假手术组间无显著性差异(P〉0.05);与起搏组KCa3.1mRNA和蛋白表达量显著下调比较,热应激组心脏各部位KCa3.1mRNA和蛋白表达量显著上调[KCa3.1蛋白,左房:(21.25±1.67)比(24.00±2.62),右房:(21.13±1.96)比(23.75±1.83),左心耳:(21.00±2.07)比(23.75±1.67),右心耳:(20.88±2.03)比(23.50±2.45)],P均〈0.05,且热应激组与假手术组间无显著差异(P〉0.05)。结论:热应激可诱导心房起搏心肌热休克蛋白(HSP)70表达上调,抑制KCa3.1mRNA和蛋白表达量显著下降。
简介:Objectives:Apoptosisisrecognizedasanimportantmechanismincontrast-inducednephropathy(CIN).Cordycepssinensis(CS),atime-honoredtonicfoodandherbalmedicineinChina,canimprovethemicrocirculation,increasethetolerancetoischemiainpatientswithmicrocirculatorydisorders.AsCShasbeenfoundtoberenoprotectiveandanti-apoptoticinmultiplekidneyinjuries,wehypothesizedthatCSwouldpreventCIN.TheobjectiveofthisresearchistostudythemechanismofCSontubularepithelialcellapoptosisindiabeticCINrats.
简介:目的探讨内皮素受体拮抗剂BQ-123对蛛网膜下腔出血(SAH)后早期脑损伤的治疗作用及其机制。方法按随机数字表法将120只SD大鼠分为假手术组、SAH组、低剂量BQ-123组(50μg/kg)和高剂量BQ-123组(75μg/kg),每组30只。采用枕大池二次注血法制作SAH大鼠模型,每组造模后进一步分为6、24、72、144h4个时间点亚组。采用光镜和电镜观察海马区形态结构变化,免疫组化和逆转录聚合酶链反应检测海马区磷脂酰肌醇3-激酶(PI3-K)、蛋白激酶B(PKB/Akt)和雷帕霉素靶蛋白(mTOR)的表达。结果(1)模型制作过程中,SAH组死亡7只,1只模型不符合标准被剔除;BQ-123高、低剂量组分别死亡6只,各组有1只模型不符合标准被剔除。最终纳入统计学分析:假手术组30只,SAH组22只,BQ-123高、低剂量组均为23只大鼠。(2)与假手术组比较,SAH组各时间点PI3-K、AKt、mTOR的表达增高(均P〈0.05)。与SAH组比较,BQ-123低剂量组海马区神经元形态结构损伤减轻,各时间点存活神经元数量增加[(132±18),(110±16),(84±13),(92±10)个/高倍视野](均P〈0.05),大鼠抓力值有所升高,学习记忆功能改善;PI3-K和Akt表达进一步升高(均P〈0.05),mTOR的表达下降(均P〈0.05)。(3)与BQ-123低剂量组各时间点存活神经元比较,BQ-123高剂量组海马区神经元形态结构损伤减轻,各时间点[存活神经元数量(153±20)、(131±18)、(137±19)、(135±17)个/高倍视野]增加(均P〈0.05),大鼠抓力值有所升高,动物学习记忆功能改善;PI3-K(3.8±0.8、8.9±2.4、8.6±2.4、6.2±2.0)、Akt(4.86±1.74、8.64±1.62、7.94±1.70、6.48±1.58)表达进一步增多(均P〈0.05),mTOR(2.89±0.26、2.14±0.18、1.94±0.17、1.62±0.12)的表达下降(均P〈0.05)。结论BQ-123对SAH后早期脑损伤有较好的治疗作用,其机制可能与调控PI3-K/Akt信号途径有关。
简介:Hypertensionisaleadingriskfactorforcardiovasculardisease,theleadingcauseofdeathandmorbidityinoursocietyandonaglobalscale.Majorcomponentsofcardiovasculardiseaseincludestroke,coronaryarterydisease,heartfailure,andchronickidneydisease,inallofwhichhypertensionplaysamajorrole.Theriskofthesecomplicationsincreasesdirectlyandlinearlywithsystolicbloodpressurestartingat115mmHg.Althoughusuallyasymptomatic,hypertensionisreadilydetectableonphysicalexaminationandisamenabletobothlifestylemodificationandpharmacologictreatmentinmostpatients.However,largeproportionsofthehypertensivepopulationremainundetectedandundertreated.Numerousguidelineshavebeenissuedduringthepastfewdecadestopromotedetectionandoptimaltherapy.Despitetheincreaseinriskwithsystolicbloodpressuregreaterthan115mmHg,thegenerallyacceptedthresholdfordiagnosisandtreatmenthasbeensystolicbloodpressuregreaterthan139mmHganddiastolicbloodpressuregreaterthan80mmHgbecauseuntilrecentlytreatmenttolowerlevelshasbeenassociatedwithanunfavorablerelationbetweenclinicalbenefitandharm.Inthepastseveralyears,newguidelines,advisories,commentaries,andclinicaltrialshaveprovidedevidenceforapotentialchangeincurrentrecommendationsforthemanagementofhypertension.Inthisregard,thelong-awaitedeighthreportoftheJointNationalCommitteeonthePrevention,Detection,Evaluation,andTreatmentofHighBloodPressurerecommendedpatientsolderthan60yearsbetreatedtoasystolicbloodpressureoflessthan150mmHg,whichhasgeneratedconsiderablecontroversyandcaution.ThestrikingfindingsoftheSystolicBloodPressureInterventionTrial(SPRINT)havereceivedconsiderableattentionbecauseofthedemonstrationthatintensivetherapytoatargetsystolicbloodpressurebelow120mmHgdecreasescardiovascularmortalityandmorbiditymorethanlessintensivetreatmenttoatargetsystolicbloodpressurebelow140mmHg
简介:ObjectivesToelucidatethepotentialroleofcytokinesinthepathogenesisofcoronaryheartdisease(CHD).MethodsTNF-αandIFN-γactivity,IL-8levelsofplasmaandsupernatantsweremeasuredin62patientswithCHDand30healthcontrolsbymethodsofdirectcytotoxicityassay,cytopathiceffectinhibitiontestandELISArespectively.ResultsBothTNF-αactivityandIL-8levelsofplasmainCHDpatientswerehigherandIFN-γactivityofsupernatantsinCHDpatientswerelowerthanthoseofhealthycontrols(P<0.001),TherehavesignificantdifferencesbetweenhealthycontrolsandthesubgroupsofCHD(P<0.01).IL-8levelsofplasmaincreasedwiththeadvancingofthediseaseandtherehaveobviousdifferencesamongsubgroupsoftheillness(P<0.05).TNF-αactivityofplasmainstableanginapectoris(SAP)subgroupwaslowerthanthoseofunstableanginapectoris(UAP)andacutemyocardialinfarction(AMI)subgroups,thedifferencesbetweenSAPandUAPorAMIweresignificant(P<0.05),ButtherehavenosignificantdifferencesbetweenUAPandAMI(P>0.05).However,IFN-γactivityofsupernatantsshowednodifferenceamonganysubgroups.ConclusionstherehavecloserelationsbetweenTNF-α,IFN-γ,IL-8andCHD.
简介:我院自1998年6月以来,采用“沈大牌”膀胱碎石镜直视下钳夹碎石治疗膀胱结石8例,效果满意,报告如下。
简介:目的探讨广谱氯离子通道阻滞剂4,4’-二异硫氰基芪-2,2’-二磺酸(DIDS)对大鼠缺血再灌注损伤心肌细胞凋亡的影响及其机制。方法雄性SD大鼠36只随机分为3组:缺血再灌注组(A组)、DIDS处理组(B组)和LY294002预处理组(C组)。伊文兰和TTC染色测定心肌梗死范围,TUNEL方法定性和定量检测心肌细胞凋亡指数,Westernblot测定蛋白激酶B(Akt)的表达。结果与A组比较,B组心肌梗死范围和心肌细胞凋亡指数明显降低[(38.8±7.7)%”(54.2±10.8)%,(8.9±1.8)%”(17.6±3.5)%.P〈0.01];磷酸化Akt表达水平明显增加(P〈0.01)。与A组比较,C组梗死面积、凋亡指数无明显减小,磷酸化Akt水平无明显变化(P〉0.05)。结论DIDS能够抑制大鼠缺血再灌注所致的心肌细胞损伤,可能是通过信号分子磷脂酰肌酶三羟基激酶/Akt的调节。