载脂蛋白A-Ⅰ模拟肽对肥胖大鼠心脏结构和功能的影响及可能机制研究

目的探讨载脂蛋白A-Ⅰ模拟肽(L-4F)对肥胖大鼠心功能的影响及可能机制。方法 50只SD大鼠中,随机选择10只喂食普通饲料为对照组,另40只喂食高脂饲料8周后,肥胖模型造模成功率75%,将肥胖模型成功大鼠30只再随机分为肥胖组、诱导剂组[血红素氧合酶1(HO-1)诱导剂L-4F]和抑制剂组(HO-1抑制剂SnMP),每组10只,各组每天腹腔注射相应药物,持续8周。心脏超声和血流动力学检测后,自腹主动脉取血,ELISA检测各项指标。苏木精-伊红染色观察心肌组织病理变化;分别用RT-PCR和Western blot测心肌组织HO-1、脂联素基因和蛋白表达。结果与对照组比较,肥胖组和抑制剂组干预8周体质量较基线体质量增加显著升高(P0.01),血糖、胰岛素、TNF-α、白细胞介素6和丙二醛水平明显升高(P0.05,P0.01),胆红素、超氧化物歧化酶[(3.26±0.51)μg/L和(5.90±0.49)μg/L vs (8.66±0.70)μg/L,P0.05,P0.01]和脂联素水平明显降低[(4.16±0.75)μg/L和(4.62±0.52)μg/L vs (6.72±1.09)μg/L,P0.05],诱导剂组上述指标无明显变化(P0.05);肥胖组和抑制剂组左心室舒张末期内径、左心室收缩末期内径显著增大(P0.01),左心室短轴缩短率和LVEF及左心室最大压力最大变化速率显著降低(P0.05,P0.01),肥胖组左心室收缩压和左心室舒张末压明显升高(P0.01),而诱导剂组上述指标则无明显变化(P0.05)。肥胖组和抑制剂组心肌组织HO-1和脂联素mRNA和蛋白表达较对照组明显减低(P0.05,P0.01);诱导剂组HO-1和脂联素蛋白表达显著高于肥胖组和抑制剂组(P0.01);而抑制剂组与肥胖组HO-1和脂联素蛋白表达无显著差异(P0.05)。苏木精-伊红染色显示,肥胖组心肌细胞肥大、充血,心肌细胞间有较明显的纤维条索形成,慢性炎性反应明显,抑制剂组心肌组织也有较明显的充血、心肌细胞肥大,纤维条索形成,但是较肥胖组减轻;诱导剂组与对照组相似。结论 L-4F上调肥胖大鼠HO-1与脂联素轴,降低肥胖大鼠体质量,减轻胰岛素抵抗和炎性反应,改善氧化应激状态,抑制心肌重构,改善肥胖大鼠的心功能。     

胸腺肽β4在大鼠心肌梗死模型中介导心脏功能保护机制

目的探讨胸腺肽β4在大鼠心肌梗死模型中介导心脏功能保护机制。方法选择雌性SD大鼠54只,通过左前降支冠状动脉结扎建立心肌梗死模型,随机分为2组:实验组大鼠腹腔内注射胸腺肽β4(5 mg/kg),对照组大鼠腹腔内注射磷酸盐缓冲液,每组27只。2～4周后心脏超声测量大鼠心功能(左心室收缩末内径、左心室舒张末内径、左心室短轴缩短率、左心室射血分数),Western blot检测梗死区生物活性蛋白因子,并测量心肌梗死面积和心肌收缩速率。结果与对照组比较,实验组大鼠注射胸腺肽β4后,心肌缺血组织中血管生长因子相关蛋白表达明显升高,心脏功能与心肌的收缩速率明显升高,而心肌梗死面积明显缩小,差异有统计学意义(P<0.05)。结论胸腺肽β4保护心脏功能防止心肌缺血后器官功能失调。     

基于Nrf2/HO-1通路研究肾素抑制剂SPH3127对两肾一夹高血压大鼠血压的影响及可能的机制

目的：探讨新型肾素抑制剂SPH3127对两肾一夹（2K1C）高血压大鼠血压的影响及可能的机制。方法：将80只雄性SD大鼠随机分为四组：假手术组、高血压模型组、SPH3127组（SPH3127 10 mg/kg干预的高血压模型）、SPH3127+全反式维甲酸（ATRA）组（SPH3127 10 mg/kg+ATRA 10 mg/kg干预的高血压模型）,每组20只。采用2K1C法建立大鼠高血压模型,按上述分组灌胃及腹腔注射给药,每日1次,连续4周。每次药物干预后2 h测量大鼠的尾动脉收缩压和舒张压,干预4周后检测血清血管紧张素Ⅱ（AngⅡ）水平,并测量胸主动脉活性氧（ROS）含量以及核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)信使RNA(mRNA)和蛋白相对表达水平。结果：经干预后,SPH3127组大鼠收缩压和舒张压较高血压模型组均显著降低（P均<0.05）。高血压模型组大鼠Nrf2、HO-1 mRNA及蛋白相对表达水平较假手术组均显著降低,SPH3127组大鼠Nrf2、HO-1 mRNA及蛋白相对表达水平较高血压模型组则显著升高,SPH3127+ATRA组大鼠应用...     

载脂蛋白A-Ⅰ模拟肽对代谢综合征大鼠心功能的可能影响及作用机制

目的探讨载脂蛋白A-Ⅰ模拟肽(L4F)对于代谢综合征(MS)大鼠通过血红素氧合酶1(HO-1)发挥作用的可能机制。方法选取大鼠60只分为对照组(20只)与MS组(40只),分别给予普通饲料与高果糖饲料喂养6周,每组各取10只行心脏超声及血流动力学检测后处死,对照组剩余10只给予碳酸铵缓冲溶液(ABCT);MS组剩余30只大鼠随机分为ABCT组、L4F组及抑制剂组,每组10只,分别给予ABCT、L4F、L4F+抑制剂,继续喂养6周,检测心肌脂联素、HO-1、磷酸化腺苷酸活化蛋白激酶(p-AMPK)、磷酸化蛋白激酶B(p-Akt)、磷酸化内皮型一氧化氮合酶(p-eNOS)表达。结果 MS组血糖、收缩压、舒张压及左心室舒张末期内径显著高于对照组(P0.05,P0.01)。与抑制剂组比较,L4F组血压、血糖、左心室舒张末压明显降低;脂联素、p-AMPK、p-Akt、p-eNOS表达显著升高(P0.05)。L4F组HO-1表达与抑制剂组相近(P0.05)。结论L4F可能是通过作用于能量代谢通路HO-1、脂联素、p-AMPK、p-Akt、p-eNOS上调HO-1的表达,降低MS大鼠血压和血糖,改善心室顺应性。     

Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死心功能的影响

目的 分析Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死(MI)心功能的影响。方法 将45只雄性SD大鼠随机分为假手术组、模型组和Notch3过表达组三组,每组各15只。大鼠心肌注射Notch3慢病毒过表达后构建MI模型。术后12周检测心功能及心脏血流动力学指标,观察心肌组织结构,并检测心肌组织Notch3和RhoA/ROCK/Hif1α轴相关蛋白水平。结果 与假手术组比较,模型组大鼠心肌组织Notch3表达水平、左心室射血分数(LVEF)、左心室舒张末压(LVEDP)显著降低,左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室收缩末压(LVESP)、左心室压力最大上升速率(LV+dp/dtmax)、左心室压力最大下降速率(LV-dp/dtmax)、心肌组织RhoA、ROCK1、ROCK2、Hif1α表达水平显著增加(P<0.05);Notch3过表达组大鼠LVESD和LVEDD显著小于模型组,心肌组织Notch3表达水平、LVEF、LVEDP显著高于模型组(P<0.05);LVESP、LV+dp/dtmax和LV-dp/dtmax、心肌...     

芪苈强心对阿霉素致心肌病大鼠心功能及血清因子的影响

目的:初步探讨芪苈强心胶囊对阿霉素致心肌病大鼠心功能及血清因子的影响及其机制。方法:将29只SD大鼠中9只作为正常对照组,20只用作造模。造模大鼠2周内分6次腹腔注射阿霉素2.5mg/kg作为心力衰竭(心衰)模型后,分为心衰组、芪苈强心组和美托洛尔组,后2组分别服用芪苈强心胶囊生粉(1g/kg)和美托洛尔(10mg/kg)治疗6周,正常对照组和心衰组以相同体积0.9%氯化钠溶液灌胃6周。超声心动图检测各组大鼠心功能指标,ELISA法检测大鼠血清肿瘤坏死因子-α(TNF-α)和B型钠尿肽(BNP)含量,心肌组织苏木素-伊红染色病理检验。结果:心衰组较正常对照组心功能显著降低,左心室收缩末期内径(LVESD)和左心室舒张末期内径(LVEDD)显著增加(P<0.01和P<0.05),左室射血分数(LVEF)和短轴缩短率(FS)显著降低(均P<0.01),血清BNP和TNF-α水平明显升高(均P<0.01)。美托洛尔组较心衰组显著改善了大鼠的LVESD、LVEDD、LVEF和FS(均P<0.05),BNP显著低于心衰组(P<0.05)。芪苈强心组较心衰组也改善了大鼠LVEF和FS(均P<0.05),显著降低心衰大鼠血...     

异丙肾上腺素对大鼠心肌缺血再灌注损伤中高迁移率族蛋白1表达的影响及机制

目的探讨异丙肾上腺素(ISO)对大鼠心肌缺血再灌注(I/R)损伤中高迁移率族蛋白1(HMGB-1)表达的影响及作用机制。方法健康雄性大鼠48只,随机分为假手术组(SO组)、I/R组、异丙肾上腺素预处理组(ISO-I/R组)、锌原卟啉Ⅸ(ZnPPⅨ)+ISO-I/R组(ZnPPⅨ组),每组12只。建立大鼠心肌I/R模型;检测各组大鼠的心肌梗死范围、肌酸激酶、乳酸脱氢酶(LDH)、TNF-α、白细胞介素(IL)6、超氧化物歧化酶(SOD)、丙二醛、血红素加氧酶1(HO-1)和HMGB-1表达的变化。结果与I/R组比较,ISO-I/R组心肌梗死面积明显缩小(P<0.01),LDH、肌酸激酶、TNF-α、IL-6、丙二醛、HMGB-1明显降低,SOD、HO-1明显升高(P<0.05);与ISO-I/R组比较,ZnPPⅨ组心肌梗死面明显扩大,LDH、肌酸激酶、丙二醛、TNF-α、IL-6、HMGB-1明显升高,SOD和HO-1明显降低(P<0.05)。结论 ISO能够明显诱导HO-1的表达并进一步抑制HMGB-1的释放,从而有效发挥对大鼠I/R损伤的心肌保护作用。     

内脏脂肪组织传入神经阻断对心肌梗死后心脏功能和心脏神经重构的影响

目的 探讨内脏脂肪组织(VAT)传入神经阻断对心肌梗死(MI)后大鼠心脏功能及心脏神经重构的影响。方法 选择SPF级健康雄性SD大鼠30只,其中12只大鼠随机分为对照组和激活组,每组6只,激活组使用低浓度辣椒素(1 mmol/L)激活VAT传入神经,对照组注射等量生理盐水,监测实时血压心率30 min,计算激活前后血压及心率变化。另外18只大鼠随机分为假手术组、MI组、高浓度辣椒素阻断组(33 mmol/L),每组6只,采用结扎冠状动脉左前降支建立MI模型。MI造模成功后高浓度辣椒素阻断组使用高浓度辣椒素阻断VAT传入神经,假手术组和MI组注射等量生理盐水。2周后通过超声心动图测定心功能,氯化三苯四氮唑染色测定MI面积,检测心肌酪氨酸羟化酶(TH)密度。生化法检测心肌丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果 激活组大鼠血压及心率变化显著高于对照组,差异有统计学意义(P<0.01)。MI组大鼠MI面积、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、心肌TH密度、心肌MDA水平显著高于假手术组,左心室射血分数(LVEF)、心肌SOD水平显著低于假手术...     

上调血红素氧合酶1对代谢综合征大鼠心功能的影响及可能机制

目的探讨钴原卟啉上调血红素氧合酶1(HO-1)对代谢综合征(MS)大鼠心功能的影响及相关机制。方法选择7周龄雄性高血压大鼠52只,分为对照组、MS组、MS+钴原卟啉组(钴原卟啉组)和MS+钴原卟啉+锡中卟啉组(锡中卟啉组),每组13只。采用Langendorff装置测量各组大鼠心脏功能和冠状动脉阻力,染色切片观察心脏横截面积和心肌纤维化程度,免疫印迹法测定心肌组织中HO-1、HO-2、环氧化酶2,氮氧化物酶2、蛋白激酶(Akt)、腺苷酸活化蛋白激酶(AMPK)、磷酸化AMPK、磷酸化Akt、脂联素、内皮型一氧化氮合酶(eNOS)、磷酸化eNOS和诱导型一氧化氮合酶(iNOS),液体闪烁计数器测量心肌超氧化物和TC水平,ELISA血浆脂联素和炎性因子水平。结果与对照组比较,MS组冠状动脉阻力明显增高(26.70±0.90 vs 19.30±0.40,P0.05)。与MS组比较,钴原卟啉组上调HO-1后不仅改善了心功能指标,脂联素、磷酸化AMPK/AMPK、磷酸化eNOS/eNOS明显增高,iNOS明显降低(P0.05)。结论上调HO-1可通过抑制氧化应激反应、炎性反应,提高脂联素水平,改善MS大鼠心功能。     

锌原卟啉对糖尿病大鼠结肠动力及Cajal细胞的影响

目的 探讨血红素氧合酶(HO)阻滞剂锌原卟啉(ZnPP)对糖尿病(DM)大鼠结肠动力和Cajal间质细胞(ICC)的影响.方法 雄性SD大鼠腹腔注射链脲佐菌素(STZ),3 d后选取成功造模大鼠24只作为DM组,另取正常大鼠16只作为对照组.饲养6周时,选取DM组大鼠和对照组大鼠各8只,行碳末推进实验,确认有无胃肠动力障碍.剩余DM组大鼠第6周起予以干预,DM未干预组(8只)0.1 mol/L磷酸盐缓冲液腹腔注射,隔日1次,连续3周;DM+ZnPP组(8只),ZnPP 10 μmol/kg腹腔注射,隔日1次,连续3周.对照组(8只)予以膜腔注射0.1 mmol/L磷酸盐缓冲液.Western印迹法检测结肠组织HO-1、HO-2和c-kit表达.免疫组化法测定结肠组织HO-1、HO-2和c-kit阳性细胞面积.结果 DM未干预组胃肠推进指数为(63.0±1.2)%,较对照组显著减低[(71.85:2.0)%,P<0.05];而DM+ZnPP组胃肠推进指数为(72.5±2.6)%,较DM未干预组明显改善(P<0.05),且与对照组差异无统计学意义(P>0.05).DM+ZnPP组近、远端结肠HO-1表达明显下降(P<0.05).DM未干预组和DM+ZnPP组近端结肠HO-2表达均较对照组显著减少(P<0.05).DM未干预组近、远端结肠组织c-kit较对照组显著减少(P<0.05);DM+ZnPP组c-kit的表达较DM未干预组明显改善(P<0.05),且与对照组间差异无统计学意义(P>0.05).结论 ZnPP可能通过阻滞HO-1对DM大鼠结肠Cajal间质细胞有保护作用,并改善其结肠动力障碍.     

西洋参叶二醇组皂苷对大鼠实验性心室重构的保护作用

目的观察西洋参叶二醇组皂苷(PQDS)对大鼠实验性心室重构的保护作用。方法结扎大鼠腹主动脉建立压力超负荷性心室重构模型。将Wistar雄性大鼠随机分为假手术组、重构模型组、阳性药贝那普利(10mg/kg)组及PQDS50、100mg/kg组。给药6w后测定心肌形态学及血流动力学参数,通过光学显微镜观察心肌病理变化。结果PQDS能明显降低心室重构大鼠的心室重量及心脏系数,明显升高收缩压(SBP)、舒张压(DBP)及平均动脉压(MAP),降低左室舒张末压(LVEDP),能抑制心肌纤维增粗,改善心肌间质水肿,其作用效果与血管紧张素转化酶抑制剂贝那普利相当。结论PQDS可能通过改善心室重构大鼠的左心收缩和舒张功能发挥防治心室重构的作用。     

心肌梗死大鼠左心室收缩与舒张功能的改变及其影响因素

目的 探讨心肌梗死大鼠左心室收缩和舒张功能的改变、以及心室重构对心室舒缩功能的影响.材料和方法结扎Wistar大鼠左冠状动脉、制成心肌梗死模型,6周后测定左室心肌力学指标,心肌胶原含量、血浆及心肌的血管紧张素Ⅱ(Aug Ⅱ)浓度.结果 心肌梗死组与对照组比较,LVPSP、+dp/dt_(max)、dp/dt_(max)绝对值及V_(max)明显降低(P<0.01),LVEDP增加(P<0.01),T值延长(P<0.01),MAP无差异.心肌梗死组与对照组比较、心肌羟脯氨酸和心肌胶原含量明显增高(P均0.01),心肌AngⅡ含量明显升高(P<0.01)、血浆AngⅡ浓度无显著差异.结论 心肌梗死后左室收缩与舒张　功能明显降低,同时出现心肌细胞的肥大和纤维细胞的增生以及间质纤维化、后者可进一步导致和加重心脏泵血功能的异常.     

Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats.

Human chymase activates not only angiotensin II but also transforming growth factor-beta, a major stimulator of myocardial fibrosis, while rat chymase activates transforming growth factor-beta, but not angiotensin II. To clarify the role of chymase-dependent transforming growth factor-beta activation, we evaluated whether chymase inhibition prevents cardiac fibrosis and cardiac dysfunction after myocardial infarction in rats. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. One day after the ligation, rats were randomized into 2 groups: 1) a chymase-treated group that received 10 mg/kg per day of the chymase inhibitor NK3201 orally for 4 weeks; and 2) a vehicle group of non-treated rats with myocardial infarction. We also included a control group who underwent sham-operation and no treatment. Four weeks after ligation, echocardiography revealed that chymase inhibitor treatment reduced the akinetic area and increased fractional area change but did not significantly change left ventricular end-diastolic area. Chymase inhibition significantly reduced left ventricular end-diastolic pressure, increased the maximal end-systolic pressure-volume relationship and decreased the time constant of left ventricular relaxation. Chymase activity in the non-infarcted myocardium was significantly increased in the vehicle group, but it was significantly reduced by chymase inhibitor treatment. The fibrotic area in the cardiac tissues and the mRNA levels of collagen I and collagen III were also significantly lower in the chymase inhibitor-treated group than in the vehicle group. Therefore, the pathway forming chymase-dependent transforming growth factor-beta may play an important role in myocardial fibrosis and cardiac dysfunction rather than left ventricular dilatation after myocardial infarction.     

血红素氧合酶-1及一氧化碳-胆红素系统对心力衰竭大鼠心功能的保护作用

目的探讨经胃肠道给予氯化高铁血红素后.体内血红素氧合酶-1(HO-1)及一氧化碳-胆红素(CO-胆红素)的反应和对大鼠慢性压力负荷性心力衰竭(心衰)进程的影响。方法将成年雄性SD大鼠63只,随机分为血红素组、心衰组和对照组,每组21只。术后3周血红素组以60 mg·kg~(-1)·d~(-1)氯化高铁血红素灌胃,另外2组同时间灌以同体积生理盐水。并分别在4、8、12周检测血清HO-1、碳氧血红蛋白(COHb);测定尾动脉压;经颈动脉插管检测平均动脉压、左心室收缩压(LVSP)、左心室舒张末压(LVEDP)以及左心室压力最大上升速率(+dp/dt_(max))和左心室压力最大下降速率(—dp/dt_(max))。结果与对照组比较,心衰组8、12周时HO-1和COHb含量明显升高(P<0.01);与心衰组比较,血红素组在4、8、12周时HO 1和COHb含量明显升高(P<0.01),8周时尾动脉压、平均动脉压和LVSP明显降低(P<0.01),8、1 2周时LVEDP明显降低(P<0.05,P<0.01),12周时±dp/dt_(max)明显升高(P<0.01)。结论经胃肠道给予氯化高铁血红素可对体内HO-1产生诱导作用;HO-1及CO-胆红素系统的诱导能减缓压力负荷性心衰大鼠心衰的进展,对心脏的收缩和舒张功能有保护作用。     

Nipradilol can prevent left ventricular systolic and diastolic dysfunction after myocardial infarction in rats.

The purpose of this study was to examine the effects of nipradilol on the cardiac function and mRNA expression in Wistar rats with a myocardial infarction (MI) that was created by ligation of the anterior descending coronary. Ten mg x kg(-1) x day(-1) of nipradilol were administrated to the rats in random order, and hemodynamic and Doppler-echocardiographic findings and myocardial mRNA expression were analyzed at 4 weeks after MI. Although left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) were increased in the MI rats, nipradilol significantly reduced the degree of the increase in both parameters. MI also significantly increased the weight of the left and right ventricles, and increased the left ventricular end-diastolic dimension (LVDd), effects that were attenuated by nipradilol. The MI rats showed decreased fractional shortening as systolic dysfunction and decreased E wave deceleration rate as diastolic dysfunction, and nipradilol significantly prevented these. Nipradilol significantly suppressed the increase in the non-infarcted myocardial mRNA expression of atrial natriuretic peptide, brain natriuretic peptide and collagen I and III. In conclusions, nipradilol prevents the cardiac remodeling that is accompanied by systolic and diastolic dysfunction, and inhibits abnormal myocardial gene expression after MI.     

Effects of growth hormone in rats with postinfarction left ventricular dysfunction

Summary Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p<0.05) and dP/dt (p<0.05) and reduced left ventricular end-diastolic pressure (p<0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure.     

重组中期因子对大鼠心肌梗死后心室重塑及Ⅲ型前胶原氨基端肽的影响

目的研究早期应用中期因子（MDK）对大鼠心肌梗死后心室重塑的作用及对Ⅲ型前胶原氨基端肽（PⅢNP）与心功能的影响。方法结扎Wistar大鼠左冠状动脉前降支建立心肌梗死动物模型。32只大鼠随机分为3组：对照组（Sham,8只）、心肌梗死组（MI,12只）和心肌梗死＋人重组中期因子干预组（MI＋MDK,12只）。造模成功后1μg／200g人重组中期因子在梗死周围分5点注射给药。4周后,所有大鼠行血流动力学、PⅢNP、微血管、胶原的测定及心脏标本的病理学分析。结果与MI组比较,MI＋MDK组的SBP、MAP、LVSP和±dp／dtmax显著增高,而LVEDP显著降低（P〈0．01）;血清PⅢNP值显著增加（P〈0．01）。病理标本分析：与MI组相比,MI＋MDK组梗死区中胶原容积分数显著增加,非梗死区中显著减少;MI＋MDK组有更多新生血管出现（P〈0．05）;MI＋MDK组炎细胞浸润、梗死面积、心肌肥大程度、心室重量明显减轻（P〈0．01）。结论急性心肌梗死大鼠早期应用MDK能发挥血管形成和胶原刺激的作用,对延缓急性心肌梗死后心室重塑发挥重要的作用。     

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.     

Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.     

Lisinopril reduces left ventricular hypertrophy and cardiac polyamine concentrations without a reduction in left ventricular wall stress in transgenic Tsukuba hypertensive mice.

This experiment was designed to determine how the angiotensin-converting enzyme inhibitor, lisinopril, acts on left ventricular wall stress and cardiac polyamine concentrations in Tsukuba hypertensive mice (THMs) carrying both human renin and angiotensinogen genes. Twelve-week-old THMs were treated with either lisinopril or hydralazine, or were left untreated, for 8 weeks. C57BL/6 mice of similar age were used as normal controls. Each group consisted of 14 mice. The systolic blood pressure of each mouse was measured once a week. Mice were euthanized at 20 weeks of age, and the left ventricular weight, left ventricular diameter, left ventricular wall stress, and left ventricular polyamine concentrations were measured. The systolic blood pressure of the untreated group was approximately 35 mmHg higher than that of the C57BL/6 mice. The left ventricular weight, left ventricular diameter, left ventricular wall stress, and left ventricular polyamine concentrations in the untreated group were significantly higher compared to those in the C57BL/6 mice. The lisinopril group had significantly decreased systolic blood pressure and other measurement items, except the left ventricular wall stress, in comparison with the untreated group. The hydralazine group also had significantly decreased systolic blood pressure and left ventricular wall stress when compared with the untreated group, but no significant differences in other measurement items when compared with the untreated group. These findings indicate that lisinopril reduces left ventricular hypertrophy and polyamine concentration without reducing left ventricular wall stress, and that simply decreasing blood pressure does not suppress left ventricular hypertrophy.