氯沙坦对慢性心力衰竭大鼠心室重塑和心功能保护作用的实验研究.doc

氯沙坦对慢性心力衰竭大鼠心室重塑和心功能保护作用的实验研究 生里垫塑l堡鱼箜第6期ChineseRemediesamp;Clinics,June2009,Vo1.9,No.6 氯沙坦对慢性心力衰竭大鼠心室重塑 和心功能保护作用的实验研究 付德明吕吉元康玉明刘卓敏 【摘要】目的研究氯沙坦(Los)对腹主动脉缩窄致慢性心力衰竭大鼠心室重塑和心功能的保护作用. 方法sD大鼠40只,随机分为腹主动脉缩窄(COA)+Vehicle组,COA+Los组,假手术(Sham)+Vehicle组.Sham+ Los组.药物干预8周后采用超声心动图和心室插管法评估心功能,计算左,右心室质量指数(LVMI,RVMI),比色 法检测心肌羟脯氨酸(HYP)含量,酶联免疫吸附试验(ELISA)检测心肌I型和Ⅲ型胶原含量和比值.放射免疫法 (RIA)检测心肌血管紧张素II(AngⅡ)和醛固酮(ALD)水平.常规苏木素一伊红(HE),Masson三色染色和透射电 镜观察心肌组织形态学改变.结果与COA组相比,COA+Los组大鼠心功能和LVMI等指标明显好转.心肌HYP 和I型胶原含量降低,I,Ⅲ型胶原比值降低;心肌AngII和ALD水平降低;心肌组织形态改变明显好转.结论 Los通过阻断AngⅡ与ATI—R结合,抑制心肌AngII和ALD生成,从而改善心肌肥厚和胶原重构所致心室重塑. 提高心功能.延缓心力衰竭进展. 【关键词】心室重构;心力衰竭,充血性;大鼠 Losartanattenuatesventricularremodelingandprotectsheartfunctionin=atswithchronicheartfailureFU De-ming,LUJi-yuan,KANGYu—ming,LIUZhuo-min.*DepartmentofCardiology,theFirstHospitalofShanxid— icalUniversity,Taiyuan030001,China 【Abstract】0bjectiveToinvestigatetheregulatoryeffectofLosartan(Les)onventricularremodelingandcflr- diacfulnctioninchronicheartfailure(CHratsinducedbyaortacoarctation(COA).MethodsFortySprague—Dawley (SD)ratswererandomizedtoreceiveabdomihalaortacoarctationtoinduceCHForshamoperationandweretreated withorallosartan(20mg?kg-1.d)orvehicle(drinkingwater).Assuchtherewerefourgroups—COA+vehiclegroup, COA+Losgroup,Sham+vehiclegroupandSham+Losgroup.Afterg-weektreatment,ultrasoundcardiographyand catheterizationwereusedtoevaluatethecardiacfunctionandleftorrightventricularmassindexfIⅣMI,RVMI).Level ofmyocardialhydmxyproline(HYP)wasmeasuredbychromometry.LevelsofmyocardiumtypeIandtypeⅢcolla- gensandtheirratioweremeasuredbyEUSA.LevelsofmyocardialangiotensinII(AnglI)andaldosterone(ALD)were measuredbyRIA.,I1lemorphologyofmyocardiumwasstudiedwithHEstaining,Masspntrichromestaining,andultra? structureofmyocardiumwasalsoobserved.ResultsLesartan—treatedCHFratshadlowerleftventricularend—dias. tolicpressure(LVEDP),higllerleftventricularejectionfraction(LVEandlowerleftventricle/bodyweightratios,low- erlevelsofmyocardiumHYP,typeIcollagen,andrelativeratioandlowerle