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。
简介:BackgroundAldosteroneblockerscouldreducetheincidenceofventriculararrhythmiasinmyocardialinfarction(MI)patientsbyregulatinghyperpolarization-activatedcyclicnucleotide-gatedchannel(HCN)expression.ButthemechanismunderlingHCNexpressionisunclear.MethodsEighteenratssurviving24hourspostMIwererandomlydividedinto3groups:MI,spironolactone,andspironolactone+antagomir-133(miRNA-133suppression).Shamgroupratshadasuturelooselytiedaroundtheleftcoronaryartery,withoutligation.HCN2andHCN4proteinandmRNAlevel,andmiRNA-133levelintheborderzoneofpost-MI1weekmyocardiumweremeasured.ResultsSpironolactonesignificantlyincreasedmiRNA-133levelsanddown-regulatedHCN2andHCN4atbothmRNAandproteinlevelsinpost-MIborderzonemyocardium.Antagomir-133reducedtheeffectsofspironolactoneonHCN2andHCN4proteinlevels.ConclusionsTheresultssuggestthatmiRNA-133isinvolvedinspironolactoneinducedHCNexpression,andpartiallycontributedtopost-MIventriculararrhythmias.
简介:BackgroundThemyocytedysfunctionmaybepresentinaorticstenosis(AS)patientswithpreservedleftventricularejectionfraction(LVEF).Earlyaorticvalvereplacement(AVR)canreversetheLVhypertrophyandimproveLVsystolicperformanceandclinicaloutcome.StrainimaginghasdemonstratedtobethemostappropriatemethodtoevaluateLVmyocardialcontractility.However,4D-strainimagingechocardiographyforthedetectionofsubclinicalleftventriculardysfunctioninASpatientswithpreservedLVEFisseldomstudied.MethodsWeprospectivelyenrolled30consecutivemoderatetosevereASpatientswithpreservedLVEF,and30healthycontrols.Conventionalechocardiographyand4D-strainimagingechocardiographywereundergoneintwogroups.The4Dstrainechocardiographicanalyseswereundertakenbyusing4DAutoLVQsoftware.ResultsComparedwiththehealthycontrols,themoderatetosevereASpatientswithpreservedLVEFhadsignificantlydecreasedglobalradialstrain(GRS),globallongitudinalstrain(GLS),globalareastrain(GAS)and4Dstrain(P<0.05),hadsignificantlyincreasedleftventricularend-diastolicvolumeindex(LVEDVI)andleftventricularmassindex(LVMI)(P<0.05),andhadlowerglobalcircumferentialstrain(GCS)(P>0.05).ConclusionsImpairedLVmyocardialcontractilityexistsinmoderatetosevereASpatients,althoughLVEFispreserved.4D-strainimagingechocardiographycandetectearlyleftventriculardysfunctioninASpatientswithpreservedLVEF.
简介:目的江西地区先心病发病率相对较高,危害百姓健康。江西省政府已从2010年始,将先心病儿童免费救治工作作为一项重要为民工程。虽然先心病病因尚不完全清楚,但近年研究发现某些基因突变与先心病发生密切相关。本课题组对局部地区(江西地区)的先心病患者进行已知致病基因(EVC,TLL1,TBX5和PTPN11)筛查,以发现与疾病密切相关和显性率高的致病基因,为将来个体化治疗提供理论基础,必将有助于局部地区乃至中国先心病出生缺陷的控制。方法从先心病DNA样本库,按照编号随机按序抽取患者DNA标本46份和100个遗传背景匹配的健康对照。根据PubMed文献报道,选择已知的4个致病基因EVC,TLL1,TBX5和PTPN11,并设计相关引物,利用DNA直接测序法四个基因的外显子及外显子-内含子进行双向测序。若核苷酸变异未在100个正常人群中发现,则定为基因突变。结果散发先心病室缺,房缺,动脉导管未闭、复杂先心分别为24例,12例,5例和5例。基因筛查发现EVC基因突变4个,分别是位于3号染色体的L115V突变,6号染色体的Y258H突变,10号染色体的K445Q突变,15号染色体的R760CQ突变,其中Y258H突变出现在房缺患者,其它3个突变见于室缺患者。发现TLL1基因多态性2个,分别是位于7号染色体的E719E,19号染色体的1991A,在房缺、室缺和PDA中均有存在。在房缺和室缺患者中发现PTPN11多态性1个,位于3号染色体的F19L。46个筛查对象中未发现TBX5基因突变和多态性。基因突变患者的临床表型与非基因突变者比,症状和体征的严重程度、发病年龄均无明显差异。结论EVC基因是江西地区间隔缺损患者的常见致病基因。突变患者的临床症状严重程度与非突变者相比无差异。由于是基因筛查工作中的前期结果,还需要后期工作中进一步增大样本量,以便对先心病患者基因型和表型的关联研究加以客观分析。
简介:目的分析心肌灌注显像时阿托品-4min腺苷负荷试验中血流动力学及心电图改变,并与4min、6min腺苷负荷试验进行比较。方法将83例研究对象分为3组:组1为阿托品-4min腺苷负荷试验组,共28例;组2为4min腺苷负荷试验组,共27例;组3为6min腺苷负荷试验组,共28例。组1在注射腺苷前10min静脉注射阿托品0.5mg。三组病例分别经肘静脉用注射泵持续注入腺苷,剂量为0.14mg·kg^-1·min^-1,用药时间为4min、4min和6min。结果①三组病例在注射腺苷3min、停药时分别与基础状态比较,血流动力学各指标变化组内比较差异有统计学意义(P〈0.001),组间差异无统计学意义。②房室传导阻滞和ST段改变在三组病例中的发生率分别为0、4%、7%和32%、33%、36%,组间比较差异均无统计学意义。结论阿托品-4min腺苷负荷试验与4min腺苷负荷试验、6min腺苷负荷试验相比,具有对心脏产生负荷、引起血流动力学变化以及相应心电图改变相同的作用,而房室传导阻滞的发生率却相对较低,有利于提高受检者对试验的耐受。
简介:目的探讨检测血清视黄醇结合蛋白4(RBP4)水平在糖尿病肾病(DN)中的意义。方法以24h尿蛋白排泄率(UAER)将118例T2DM患者分为三组,用酶联免疫吸附法(ELISA)测定其血清RBP4水平,并以40例健康人作对照。结果T2DM非DN组、早期DN组及临床DN组的血清RBP4水平均明显高于对照组(均P<0.05),且与Scr,UAER和TG呈显著正相关(r=0.35、0.69、0.28,均P<0.05),与eGFR呈显著负相关(r=-0.44,P<0.05);多元线性逐步回归分析发现Scr是血清RBP4的独立相关因素(B=2.41,P<0.05)。结论血清RBP4水平检测对于判断DN患者病情及预后有一定意义。
简介:Previousstudiessuggestthatreductionanddysfunctionofcirculatingendothelialprogenitorcells(EPCs),anddysregulationinstromalcellderivedfactor-1/CXC-chemokinereceptor4(SDF-1/CXCR4)axisindiabetescouldbetherapeutictargetsfordiabeticischemicstroke.ThisstudyinvestigatedtheefficacyofCXCR4-primingEPCsoncerebralrepairfollowingischemicstrokeindb/dbdiabeticmice.BonemarrowderivedEPCsfromdb/+controlmiceweretransfectedwithadenovirus(1×10~7IU)carryingCXCR4(Ad-CXCR4-EPCs)ornull(Ad-null-EPCs).Thedb/dbmiceweredividedintothreegroupsforEPCsinjection(2×10~5cells/100μl):Ad-CXCR4-EPCs,Ad-null-EPCsorsaline(vehicle),viatailvein2hrsaftermiddlecerebralarteryocclusion(MCAO)surgery.Cerebralbloodflow(CBF)wasmeasuredwithlaserDopplerflowmeter.Miceweresacrificedat2or7daysthereafter.LevelofcirculatingEPCswasmeasuredbyflowcytometry.Ischemicdamage,cerebralmicrovasculardensity(MVD),angiogenesisandneurogenesisweredeterminedbyhistologicalstainingwithFluoro-J,CD31,CD31+BrdU,NeuN+BrdU,GFAP+BrdU,respectively.Results(table)showed:1)LevelsofCXCR4expressionwerereducedinthebrainandEPCsofdb/dbmiceasmeasuredbyreal-timeRT-PCRandwesternblotanalyses(datanotshown);2)ThelevelofcirculatingEPCswasmoreinthemicetreatedwithAd-CXCR4-EPCs;3)EPCtransfusionimprovedCBF,increasedMVD,angiogenesisandneurogenesisinperi-infarctarea,anddecreasedischemicdamage.TheefficacieswerebetterinAd-CXCR4-EPCsgroup.DatasuggestthattransfusionofAd-CXCR4-EPCscouldbeatherapeuticavenueforischemiastrokeindiabetes.