血管紧张素转换酶抑制剂和AT1受体拮抗剂联合应用对大鼠心室重构影响的实验研究

目的　利用大鼠心肌梗死 (MI)模型 ,探讨福辛普利 (ACEI)、AT1受体拮抗剂 (依贝沙坦 )及二者合用防治心室重构的作用及机制。方法　 2 0 0 3- 0 3～ 2 0 0 3- 0 6将心肌梗死 (MI)后 2 4h大鼠随机分组。 6周后查 :平均动脉压、左室舒张末压 ;心室重量 /体重 ;非梗死区总胶原、Ⅰ型及Ⅲ型胶原所占面积的百分比及非心肌细胞增生数 ;转化生长因子 (TGF β1)mRNA表达。结果　依贝沙坦组和两药合用组总胶原含量较福辛普利组降低更明显 ;两药合用组I型胶原含量和非心肌细胞增生数低于福辛普利组。依贝沙坦组和两药合用组与安慰剂组相比TGF β1mRNA表达降低。结论　两药单独及联合应用可抑制心肌肥大及胶原沉积 ;在抑制胶原沉积上依贝沙坦及联合用药较福辛普利效果更佳 ;依贝沙坦及两药合用可使TGF β1mRNA表达降低 ;两药合用较福辛普利单用有更强的抑制非心肌细胞增生的作用。     

Smad表达与心肌梗死后心室重构的关系

目的研究Smad3、Smad7表达与心肌梗死后大鼠心室重构的关系。方法冠状动脉结扎建立心肌梗死模型,假手术组为对照,8周后处死大鼠。测量心室重量／体重,血液动力学,非梗死区胶原含量,逆转录聚合酶链反应检测大鼠心肌各部位转化生长因子（TGF）β1 mRNA、Smad3 mRNA、Smad7 mRNA的表达。结果与假手术组相比,心室重量／体重,左室舒张末压,非梗死区胶原含量均增加;梗死区、梗死边缘区、非梗死区及右室TGFβ1 mRNA和Smad3 mRNA的表达增加,而Smad7 mRNA表达降低。结论TGFβ-Smad传导通路参与心肌梗死后的心室重构过程。Smad3对心室重构有促进作用,而Smad7对心室重构有抑制作用。     

替米沙坦对大鼠心肌梗死后心室重构的影响

目的 研究替米沙坦对心肌梗死后心室重构的影响.方法 应用冠状动脉结扎法建立大鼠心肌梗死(M1)模型,24h后存活大鼠随机分为安慰剂对照组和替米沙坦治疗组,另设假手术组.8 w后,测量心室重量/体重(HW/BW),非梗死区胶原含量,多普勒超声评价心脏功能.结果 对照组与假手术组比较HW/BW、左心室舒张末期内径(LVDd)、E/A比值、非梗死区胶原含量、射血分数(EF)、短轴缩短率(FS)、后壁(PW)增厚率均降低(均P＜0.01).治疗组与对照组比较,上述指标显著改善(均P＜0.01).结论 替米沙坦可抑制并减轻M1后左室重构.     

人参皂苷Rb1对急性心肌梗死大鼠心室重构的影响

目的通过大鼠急性心肌梗死心室重构模型观察人参皂苷Rb1对心室重构的影响.方法结扎雄性SD大鼠左冠状动脉前降支制备急性心肌梗死(AMI)模型,随机分为AMI对照组(n=7)和人参皂苷Rb1治疗组(n=8,简称Rb1治疗组),另设假手术组(n=8).Rb1治疗组经腹腔注射人参皂苷Rb1(4mg·kg-1·d-1),假手术组及AMI对照组给予同量的0.9%氯化钠溶液,4周后检测大鼠血流动力学及形态学参数,免疫组化法检测左室非梗死区Ⅰ型胶原表达.结果与假手术组比较,AMI对照组左室重量指数、左室截面直径、Ⅰ型胶原含量及左室舒张末压(LVEDP)均明显增高,差异有非常显著性意义(P＜0.01),而左室收缩压(LVSP)及左室内压最大上升和下降速率均明显降低,差异有非常显著性意义(P＜0.01);与AMI对照组比较,Rb1治疗组左室重量指数、左室截面直径、Ⅰ型胶原含量及LVEDP、左室梗死面积均明显降低,差异有显著性意义(P＜0.01 或＜0.05),而LVSP及左室最大上升和下降速度均明显增高,差异有显著性意义(P＜0.05).三组间心率差异无显著性意义.结论人参皂苷Rb1能有效抑制急性心肌梗死大鼠的心室重构,保护心功能.     

氟伐他汀对急性心肌梗死后左室重构的实验研究

目的观察氟伐他汀对急性心肌梗死兔早期左室重构和心功能的影响。评价C反应蛋白（CRP）对心肌梗死后左室重构的预测价值。方法将梗死后24h存活兔随机分成：AMI模型组（M组，n=11），AMI氟伐他汀组（F组，n=12），另设假手术组（S组，n=10）。给药2周后，测血流动力学参数，比较各组间左室重构各指标。结果与假手术组相比，AMI模型组左室舒张末压（LVEDP）、左室重量（LVW）、左室重量指数（LVWI）、血CRP均显著增加（P＜0．05），左室收缩压（LVSP）、左室内压最大上升和下降速率（±dp／dtmax）均显著降低（P＜0．05）。与AMI模型组相比，AMI氟伐他汀组LVEDP、LVW、LVWI、血CRP均显著降低（P＜0．05），LVSP、±dp／dtmax均显著增加（P＜0．05）。结论氟伐他汀减少心梗后CRP的作用可能是其减轻急性心肌梗死后早期左室重构的机制之一。高浓度血CRP是预测心肌梗死急性期发生心室重构的预测因素。     

血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白表达及胶原沉积的影响

目的:探讨血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白(OPN)的表达及心肌间质胶原沉积的影响。方法:将心肌梗死后24小时存活大鼠随机分为两组:盐水组(16只,5ml/d),厄贝沙坦组[17只,45mg/(kg·d)];另设假手术组(15只)作对照。分别于心肌梗死后4周:导管法测定左心室有创血流动力学及心功能;组织学方法检测非梗死区胶原纤维沉积和心肌细胞横径;Western blot法检测心肌组织骨桥蛋白表达。结果:盐水组与厄贝沙坦组大鼠梗死面积相似,无显著性差异(P>0.05);假手术组大鼠心肌组织Western blot法未检测到骨桥蛋白表达,盐水组大鼠心肌组织有大量骨桥蛋白表达,该上调的蛋白能被厄贝沙坦治疗显著抑制(P<0.01)。与假手术组相比,所有心肌梗死大鼠均出现显著的心肌间质纤维沉积,左心室相对重量增大,非梗死区心肌细胞横径增加,均有显著性差异(P均<0.01);与盐水组相比,厄贝沙坦组心肌间质纤维沉积减轻,左心室相对重量及非梗死区心肌细胞横径降低,均有显著性差异(P均<0.01)。与假手术组相比,所有心肌梗死大鼠在4周后均表现出左心室收缩压和左心室压力最大上升和下降速率显著下降,左心室舒张末压显著上升,均有显著性差异(P均<0.01),提示了显著的左心室收缩和舒张功能不全;与盐水组相比,厄贝沙坦组大鼠心功能显著改善,均有显著性差异(P均<0.01)。结论:心肌梗死后大鼠心肌组织出现大量骨桥蛋白表达,厄贝沙坦治疗显著抑制心肌梗死大鼠骨桥蛋白的表达,并能改善心肌的纤维化,改善心脏功能。     

咪达普利对陈旧性心肌梗死非梗死区心肌跨室壁复极离散度及短暂外向钾电流的影响

目的 探讨咪达普利对陈旧性心肌梗死非梗死区心肌跨室壁复极离散度（TDR）以及短暂外向钾电流（Ito）的影响。方法24只兔随机分为3组,两组结扎左冠状动脉回旋支制成心肌梗死模型,手术后1周1组给予咪达普利 0.625mg·kg-1·d-1口服（咪达普利组）,另1组则给予安慰剂口服（陈旧性心肌梗死组）;第3组开胸但不结扎冠状动脉也给予安慰剂口服（假手术组）。3个月后酶解分离得到左心室壁远离梗死中心区的3层心肌单细胞（心外膜下心肌细胞、中层心肌细胞和心内膜下心肌细胞）,用膜片钳技术研究跨室壁复极离散度（TDR）以及3层心肌细胞的短暂外向钾电流（Ito）的改变。结果 心肌梗死后3个月,非梗死区的心肌细胞发生了肥厚和重构,3层心肌细胞的动作电位时限（APD）明显延长,其中心内膜下心肌细胞的APD明显短于心外膜下心肌细胞和中层心肌细胞（P<0.01）,与假手术组对比呈相反的跨室壁离散。陈旧性心肌梗死TDR也明显增加,但TDR在咪达普利组和假手术组间差异不明显。陈旧性心肌梗死3层心肌细胞的Ito密度均降低,以心外膜下心肌细胞和中层心肌细胞较明显（P<0.05）,咪达普利组和假手术组相比,Ito密度无明显改变（P>0.05）。结论陈旧性心肌梗死远离梗死中心区的左心室心肌细胞发生代偿性肥厚,APD延长,TDR增加,3层心肌细     

脑钠肽静脉滴注抑制大鼠心肌梗死后的心室重构

目的验证和比较持续静脉滴注外源性脑钠肽（BNP）和依那普利灌胃对于心肌梗死后心室重构的抑制作用,并观察其对心肌基质金属蛋白酶（MMPs）的影响。方法 SD大鼠随机分为4组：假手术组;对照组;心肌梗死＋依那普利[10mg/（kg·d）]灌胃治疗组;心肌梗死＋脑钠肽[0.06μg/（kg·min）]持续静脉微泵推注治疗组。应用超声心动图、免疫组化、ELISA和Western blot等方法评估各组的心室重构和心功能状况。结果 BNP和依那普利可抑制大鼠心肌梗死后左室质量指数的增加（分别减少13.2%和16.9%,P〈0.05）,改善心肌梗死后大鼠的左室舒张未压（分别降低33.0%和45.8%,P〈0.05）。超声心动图结果提示,给予BNP和依那普利持续治疗28天后,其左室舒张末径（LVEDD）大小和左室短轴收缩率（FS）优于对照组[LVEDD：对照组（8.8±0.6）mm,依那普利组（7.5±0.7）mm,脑钠肽组（7.5±1.0）mm,P〈0.05;FS：对照组（19.2±2.6）%,依那普利组（27.7±5.6）%,脑钠肽组（27.5±3.9）%,P〈0.05]。依那普利和BNP都能够明显抑制心肌梗死后期非梗死区的胶原、特别是Ⅰ型胶原的增生[对照组（6.8±1.4）%,依那普利组（4.0±0.9）%,脑钠肽组（3.7±1.1）%;P〈0.05]。静脉输注BNP治疗可升高心肌的cGMP含量,但抑制心肌血管紧张素Ⅱ的作用不及依那普利。BNP对非梗死区MMP-2和MMP-9含量无明月显影响。结论心肌梗死后持续静脉给予BNP可能通过cGMP介导的信号途径发挥其心脏保护作用,包括抑制心肌梗死后的心脏肥厚、心室扩大,改善心功能,减少非梗死区心肌胶原沉积,对非梗死区MMP-2和MMP-9的表达并无明显影响。     

缬沙坦对大鼠急性心肌梗死后左室重塑的影响

目的研究缬沙坦对大鼠急性心肌梗死(AMI)后左室重塑的影响。方法将冠脉结扎术后24 h的SD大鼠随机分为心梗组、缬沙坦小剂量组(10 mg·kg-1·d-1)和缬沙坦大剂量组 (30 mg·kg-1·d-1)组,另设假手术组。灌胃给药四周后测定以下指标:(1)左心功能;(2)体重 (BW)、左心室重量(LVM)及左室重量指数(LVMI);(3)心肌梗死面积;(4)左室非梗死区胶原容积分数(CVF。)。结果各心梗组间的心肌梗死面积无显著差别(P>0．05)。与假手术组相比,心梗组左室舒张末压(LVEDP)、INM、LVMI及CVF明显增大,左室收缩压(LVSP)和心室内压最大变化速率 (±dp／dtmax)明显降低(P均<0．01)。与心梗组相比,大剂量缬沙坦可使LVEDP明显降低,±dp／ dtmax明显升高(P<0．01),小剂量缬沙坦对心梗大鼠心功能影响不明显。两种剂量缬沙坦都可明显降低心梗大鼠LVM、LVMI及左室非梗死区CVF,且大剂量缬沙坦较小剂量更显著。结论缬沙坦能够抑制大鼠AMI后的左室肥厚及非梗死区胶原沉积,改善AMI后的左室重塑。     

凋亡基因在心肌梗死的表达及血管紧张素转化酶抑制剂的干预作用

目的探讨凋亡基因对大鼠心肌梗死的表达及血管紧张素转化酶抑制剂(ACEI)的干预作用。方法将大鼠随机分为假手术组、梗死模型组、梗死模型 福辛普利小剂量组、梗死模型 福辛普利大剂量组,用逆转录-聚合酶链反应(RT-PCR)方法检测大鼠心肌梗死24h和4周时心肌细胞内凋亡抑制基因Bcl-2与凋亡基因Bax、P53、Fas的mRNA表达量,并探讨它们之间的相互关系。结果急性心肌梗死24hBcl-2表达下降,福辛普利促进其高表达,Bax、P53、Fas增高,福辛普利抑制其表达;急性心肌梗死4周,Bcl-2表达下降,福辛普利促进其表达,Bax、P53表达变化不大,福辛普利对其表达无影响,Fas高表达,福辛普利抑制其表达。结论大鼠急性心肌梗死后心肌细胞存在凋亡现象,Bcl-2表达下降,Bax、P53、Fas表达上调介导心肌梗死后心肌细胞凋亡的发生。ACEI可通过干预上述基因抑制急性心肌梗死后的心肌细胞凋亡。     

Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction

OBJECTIVES: The mechanisms underlying the clinical benefits of mineralocorticoid receptor antagonism in patients with left ventricular (LV) dysfunction and heart failure (CHF) after myocardial infarction (MI) are poorly understood. METHODS: We investigated whether long-term (9 weeks) aldosterone antagonism with eplerenone (100 mg/kg/day) provides additional benefit to angiotensin II type 1 (AT1) receptor inhibition with irbesartan (50 mg/kg/day) on cardiac remodeling after MI in rats. RESULTS: Eplerenone monotherapy, like AT1 receptor blockade, significantly reduced LV end-diastolic pressure (LVEDP), end-systolic volume (LVESV) and end-diastolic volume (LVEDV) compared to placebo. Improvement of LV dilation by aldosterone antagonism was associated with a significant reduction of increased AT1 receptor, angiotensin-converting enzyme (ACE) and endothelin-1 gene expression in the noninfarcted LV myocardium. Combination therapy with irbesartan led to a substantial further leftward shift of the LV pressure-volume curve and decrease in LVEDP, LVESV and LVEDV. Moreover, combination therapy significantly improved LV systolic and diastolic function and reversed LV alterations of alpha- and beta-myosin heavy-chain isoforms, ANF and SERCA2 ATPase expression more effectively than monotherapies. LV collagen type I and type III expression as well as interstitial fibrosis were substantially increased in placebo CHF rats, similarly decreased by eplerenone and irbesartan, and further reduced by eplerenone/irbesartan. However, no additive effects of eplerenone/irbesartan on myocardial AT1 receptor, ACE and endothelin-1 mRNAs were observed. CONCLUSIONS: Aldosterone receptor antagonism provides additional benefit to AT1 receptor blockade on LV function and remodeling associated with improvement of molecular alterations responsible for progressive contractile dysfunction post-MI.     

心肌肥厚的PTEN负性调控与卡托普利干预对其影响的实验研究

目的检测异丙肾上腺素(isoproterenol,ISO)诱导的心肌肥厚大鼠PTEN mRNA、蛋白水平表达及卡托普利(captopril,Cap)对其表达的影响,从而探讨PTEN的负性调控在心肌肥厚中的作用。方法24只大鼠随机分为对照组、ISO组、Cap+ISO组。利用小剂量ISO持续背部皮下注射大鼠,建立心肌肥厚模型。在观察期末,分别测定各组大鼠体重、心脏湿重、左室湿重,计算出心脏重量/体重及左室重量/体重;电镜观察超微结构的变化,并测定左室收缩末压、左室舒张末压、左心室压力上升及下降最大速率等指标。RT-PCR测定心肌组织PTEN mRNA,Western blot测定其蛋白表达。结果(1)与对照组比较,ISO组、Cap+ISO组的左室重量/体重、心脏重量/体重、左室收缩末压、左室舒张末压均升高(P≤0.05),左室压力上升及下降最大速率(±dp/dtmax)均下降(P≤0.05)。(2)与ISO组相比,Cap+ISO组的左室重量/体重、心脏重量/体重、左室收缩末压、左室舒张末压均下降(P≤0.05,P≤0.01),左室压力上升及下降最大速率(±dp/dtmax)均升高(P≤0.05,P≤0.01)。(3)与对照组比较,ISO组、Cap+ISO组的PTEN mRNA、蛋白表达均增加。(4)与ISO组比较,Cap+ISO组的PTEN mRNA、蛋白表达增加。结论ISO诱导心肌肥厚PTENmRNA、蛋白表达升高,心肌肥厚过程中存在负性调控,PTEN是一种内源性抑制心肌肥厚的重要因子。卡托普利不仅能明显抑制心肌肥厚,改善血液动力学参数,而且还能上调心肌PTEN水平,这是其抑制心肌肥厚的又一机制。     

Combination Angiotensin Converting Enzyme and Direct Renin Inhibition in Heart Failure following Experimental Myocardial Infarction

Aims: Diminishing the activity of the renin–angiotensin system (RAS) plays a pivotal role in the treatment of heart failure. In addition to angiotensin converting enzyme (ACE) inhibitors and angiotensin‐receptor blockers, direct renin inhibition has emerged as a potential adjunctive treatment to conventional RAS blockade. We sought to determine the effectiveness of this strategy after myocardial infarction (MI) in the setting of preexisting hypertension, a common premorbid condition in patients with ischemic heart disease. Methods and Results: Ten‐week‐old female heterozygous hypertensive (mRen‐2)27 transgenic rats (Ren‐2), were randomized to one of five groups (n = 8 per group); sham, MI, MI + aliskiren, MI + lisinopril and MI + combination lisinopril and aliskiren. Cardiac function was assessed by echocardiography and in vivo cardiac catheterization. Untreated MI animals developed heart failure with hypotension, dilation, reduced ejection fraction (EF), and raised left ventricular end‐diastolic pressure (LVEDP). Treatment with single agent treatment had only modest effect on cardiac function though combination therapy was associated with significant improvements in EF and LVEDP when compared to untreated MI animals (P < 0.05). Histologic analysis demonstrated increase extracellular matrix deposition and cardiomyocyte hypertrophy in the noninfarct region of all MI groups when compared with sham operated animals (P < 0.05) that was reduced by ACE inhibitor monotherapy and combination treatment but not by aliskiren alone. Conclusion: In a hypertensive rat model that underwent experimental MI, EF, and LVEDP, key functional indices of heart failure, were improved by treatment with combination ACE and direct renin inhibition when compared with either agent used alone.     

Effects of spironolactone and fosinopril on the spontaneous and chronic ventricular arrhythmias in a rat model of myocardial infarction.

We documented chronic ventricular arrhythmias in a first group of 58 rats after myocardial infarction (MI), then assessed the effects of spironolactone and fosinopril on morphological indexes and arrhythmias in a second group (n = 33). Rats underwent Holter monitoring at 2 months after MI. Treatment was randomly given from 1 until 4 months after MI: placebo in 12 rats (P), fosinopril in 9 (F) and spironolactone + fosinopril in 12 (SF). The score of ventricular premature beats (VPBs) was related to the MI size and the delay from MI (p < 0.01). VPB's reduction/increase required to demonstrate anti/pro-arrhythmic effects were 55 and 59%. Mass indexes were lower in F and SF (p = 0.01). VPB's difference (4 months vs. 1) was positive in P, significantly lower in F and negative in SF (p = 0.04). In this relevant model of spontaneous and chronic ventricular arrhythmias, SF association did not increase mortality but lowered the arrhythmic score.     

骨髓间充质干细胞对大鼠梗死心肌胶原重构的双重调节作用

目的 探讨骨髓间充质干细胞(MSC)对梗死心肌胶原重构的调节作用。方法 采用结扎冠状动脉前降支的方法复制大鼠心肌梗死(MI)模型,随机分为假手术组（仅穿线不结扎冠状动脉,n=8）、MI+ PBS组（结扎冠状动脉+心肌注射PBS溶液,n=8）和MI+ MSC组（结扎冠状动脉+心肌注射MSC,n=8）。通过心脏超声检查、血液动力学检查和组织学染色方法分别检测左心室射血分数(LVEF)、短轴缩短率(FS)、左心室收缩末压力(LVSP)、左心室舒张末压力(LVEDP)、左心室压最大升降速率（±dp/dtmax）、心肌梗死面积和梗死扩张指数等指标,评价MSC对大鼠心功能及心室重构的影响。同时采用免疫组化、RT-PCR、Western blot等方法,测量胶原蛋白表达情况。结果 (1)MI大鼠心室重构和心脏功能指标的检测结果：MI+ MSC组大鼠心肌梗死面积显著小于MI+ PBS组[(38.27±2.70)％比(46.20±3.17)％,t=5.386,P＜0.001],FS显著高于MI+ PBS组[(29.98±4.50)％比(23.43 ±3.34)％,t=-3.305,P=0.005],LVSP显著高于MI+ PBS组[(113.63±10.81)mm Hg(1 mm Hg=0.133 kPa)比（99.25±16.76）mm Hg,P＜0.05],LVEDP显著低于MI+PBS组[(12.10±4.28) mm Hg比(20.08±4.26) mm Hg,P＜0.05],+dp/dtmax显著高于MI+ PBS组[（4616.63±363.34）mum Hg/s比(3912.75±248.79) mm Hg/s,P＜0.05],- dp/dtmax显著高于MI+ PBS组[(4254.63±324.34) mm Hg/s比（3530.88±309.71）mm Hg/s,P＜0.05]。(2)Ⅰ型和Ⅲ型胶原蛋白表达水平的检测结果：MI+ MSC组大鼠梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著高于MI+ PBS组,而非梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著低于MI+ PBS组（P均＜0.05）。结论 MSC通过促进MI大鼠梗死区胶原蛋白修复性合成,减少非梗死区胶原蛋白沉积,从而抑制心室重构,改善心脏功能。     

Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction

OBJECTIVES: We investigated the effects of the aldosterone blocker eplerenone alone and in combination with angiotensin-converting enzyme (ACE) inhibition on ventricular remodeling in rats with left ventricular (LV) dysfunction after extensive myocardial infarction (MI). BACKGROUND: Adding an aldosterone antagonist to ACE inhibition reduces mortality and morbidity in heart failure. METHODS: Starting 10 days after MI, rats were treated with placebo, eplerenone (100 mg/kg/day), the ACE inhibitor trandolapril (0.3 mg/kg/day), or a combination of both for nine weeks. RESULTS: Both monotherapies attenuated the rise in LV end-diastolic pressure (LVEDP) and LV end-diastolic volume (LVEDV) compared with placebo, whereas combined treatment further attenuated LVEDP and LVEDV, significantly improved LV function and reduced plasma norepinephrine levels. The time constant of LV pressure isovolumic decay (tau) was prolonged in placebo MI rats, significantly shortened by eplerenone, and normalized by eplerenone/trandolapril. Increased collagen type I gene expression and collagen content in the noninfarcted LV myocardium from MI placebo rats was attenuated by trandolapril, but almost completely prevented by eplerenone and eplerenone/trandolapril. The addition of eplerenone to ACE inhibition prevented sarcoplasmic-reticulum calcium ATPase downregulation and the increases in LV gene expression of beta-MHC and atrial natriuretic factor more effectively than either monotherapy. Furthermore, combination treatment attenuated the increase in myocardial angiotensin II type 1 receptor expression and increased phosphorylated endothelial nitric oxide synthase protein levels. CONCLUSIONS: The aldosterone blocker eplerenone improved LV remodeling in rats with LV dysfunction after extensive MI. Combination therapy with an ACE inhibitor substantially potentiates this effect by a complementary prevention of LV fibrosis, cardiac hypertrophy, and molecular alterations.     

携带人B型利钠肽基因重组腺病毒对慢性心力衰竭大鼠心功能的影响

目的 观察外源基因人B型利钠肽对慢性心力衰竭(心衰)大鼠心功能的影响.方法 30只入选心衰大鼠,随机分为携带人B型利钠肽基因重组腺病毒组(Ad-hBNP组)、重组空白腺病毒组(Ad-Track组)、生理盐水组(NS组),另设不予任何治疗的假手术组作为对照;分别经腹腔注射予以相应治疗,每周1次,共4周.4周后实验动物行超声心动图、血流动力学检测,酶联免疫吸附试验检测血清外源基因人B型利钠肽水平,全心质量指数检测.结果 间断Ad-hBNP治疗后,Ad-hBNP组心衰大鼠室间隔厚度、左室后壁厚度、左室舒张末径、左室收缩末径[(2.34±0.29)mm、(2.28±0.18)mm、(6.50±0.42)mm、(3.54±0.59)mm]显著低于Ad-Track组[(2.71±0.35)mm、(3.02±0.85)mm、(7.71±0.83)mm、(4.72±0.80)mm,均为P＜0.05]和NS组[(2.78±0.23)mm、(2.83±0.53)mm、(7.34±0.97)mm、(4.55±0.77)mm,均为P＜0.05],而左室射血分数、左室短轴缩短率[(79.27±7.01)%、(43.38±6.73)%]显著高于Ad-Track组[(70.85±4.81)%、(35.72±3.68)%,均为P＜0.01]和NS组[(69.67±6.90)%、(34.91±5.10)%,均为P＜0.01].Ad-hBNP组与Ad-Track组和NS组比较:心率显著降低,左室收缩压显著升高[为(131.79±15.76)mm Hg(1 mm Hg=0.133 kPa)、(112.99±32.35)mm Hg、(117.13±15.26)mm Hg],左室内压最大上升速率显著升高[分别为(5037.20±430.41)mm Hg/s、(4217.40±1354.15)mm Hg/s、(4310.50±1293.97)mm Hg/s;P＜0.05];左室内压最大下降速率显著升高[分别为(-4382.00±1304.79)mm Hg/s、(-3725.00±791.34)mm Hg/s、(-3890.00±1043.73)mm Hg/s,均为P＜0.05];左室舒张末压降低[分别为(-4.24±4.00)mm Hg、(21.99±6.80)mm Hg、(18.00±12.25)mm Hg,均为P＜0.01];心脏质量及全心质量指数均降低.结论 间断给予Ad-hBNP能够有效地改善心衰大鼠心脏结构和功能.

Abstract：

Objective To evaluate the therapeutic effect of hBNP on rats with chronic heart failure (CHF). Methods Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2. 5 × 1010 VP/ml NS Ad-hBNP 1 ml/week ×4,n = 14), Ad-Track group ( n = 8 ), placebo group ( NS, n = 8 ), 10 sham-operated rats served as control group. After 4 weeks treatment, cardiac function was evaluated by echocardiography and hemodynamic measurements. Heart weight (HW) and HW/body weight (BW) ratio were determined. Results IVS,LVPW, LVEDD and LVESD were significantly reduced in the Ad-hBNP group [(2. 34 ±0. 29)mm, (2. 28 ± 0. 18)mm, (6. 50 ±0. 42)mm, (3.54 ±0. 59) mm] than those in the Ad-Track group[(2. 71 ±0. 35) mm,(3.02 ±0.85)mm, (7.71 ±0.83)mm, (4.72 ±0.80)mm] and in the NS group [(2.78 ±0.23)mm,(2. 83 ± 0. 53 ) mm, (7. 34 ± 0. 97 ) mm, (4. 55 ± 0. 77 ) mm, all P ＜ 0. 05]. The LVEF and LVFS of the Ad-hBNP group [(79. 27 ±7.01 )%, (43.38 ±6. 73)%] were significantly higher than in the Ad-Track group[(70.85±4.81)%, (35.72 ±3.68)%] and in the NS group[(69.67 ±6.90)%, (34.91 ±5.10)%, all P ＜0. 01]. HR[(417.48 ±32. 57) beats/min, (446. 85 ±61.49) beats/min, P ＜0. 05;(440. 83 ±32. 18) beats/min , P ＜0. 05], LVEDP[( - 4. 24 ±4. 00) mm Hg( 1 mm Hg =0. 133 kPa);(21.99 ±6. 80) mm Hg, P ＜0. 01; ( 18.00 ± 12. 25)mm Hg, P＜0. 01] were significantly decreased and while LVSP[(131.79 ±15.76) mm Hg; (112.99 ±32.35) mm Hg, P＜0.05; (117.13 ±15.26)mmHg], +dP/dtmax[(5037.20 ±430.41) mm Hg/s; (4217.40 ± 1354. 15)mm Hg/s, P ＜0.05;(4310. 50 ± 1293.97 ) mm Hg/s, P ＜ 0. 05] and - dP/dtmax [( - 4382. 00 ± 1304. 79 ) mm Hg/s;(-3725.00±791.34) mm Hg/s, P ＜ 0.05; ( - 3890.00 ± 1043.73) mm Hg/s, P ＜ 0.05] were significantly increased in Ad-hBNP group than in Ad-Track group and NS group ( all P ＜ 0. 05 ). HW and HW/BW were also decreased in Ad-hBNP group than in the Ad-Track group and the NS group. Conclusion Exogenous hBNP improved the cardiac function and attenuated remodeling in CHF rats.     

福辛普利对糖尿病大鼠心肌血栓素蛋白1mRNA和蛋白质表达的影响

目的研究福辛普利对链脲佐菌素诱导的糖尿病大鼠心肌组织血栓素蛋白1（TSP-1）表达的影响。方法30只13周龄健康雄性SD大鼠,腹腔注射1％链脲佐菌素（STZ）,随机区组法分为糖尿病组（无药物干预,其中8周末组10只,12周末组10只）和福辛普利组（蒙诺片,10mg·kg^-1·d^-1,10只）,另选8只健康雄性SD大鼠（等量蒸馏水腹腔注射）作为正常对照组。糖尿病组于8周末处理大鼠10只,余10只与福辛普利组及对照组于12周末时处理,免疫组化检测心肌间质Ⅰ、Ⅲ型胶原与转化生长因子-β1（TGF-β1）蛋白表达水平,心肌组织TSP-1蛋白表达和血管紧张素Ⅱ（AngⅡ）水平;RT．PCR检测心肌组织TSP-1mRNA表达水平。多个样本均数的比较采用单因素方差分析,两两比较采用q检验。结果与对照组比较,心肌细胞TSP-1阳性表达率增加（0．94±0．03VS0．15±0．02,P〈0．05）;AngⅡ水平增加（11．33±0．97VS6．11±0．48,P〈0．05）。心肌间微血管壁上TSP-1阳性表达光密度值与对照组比较无统计学差异。心肌细胞TSP-1表达阳性率低于12周末糖尿病组（0．30±0．02VS0．95±0．01,P〈0．05）。RT—PCR结果显示,心肌TSP-1mRNA水平在糖尿病组增加（2．01±0．41VS0．95±0．01,P〈0．05）,而在福辛普利组减轻（1．02±0．01VS2．25±0．21,P〈0．05）。结论糖尿病性大鼠心肌间质纤维化严重可能与心肌组织水平高表达AngII及过表达TSP-1有关;福辛普利通过降低AngⅡ及TSP-1水平,下调TGF—β1活性,抑制心肌纤维化进程。     

依那普利,福辛普利对自发性高血压大鼠心肌超微结构逆转的实验研究

目的：观察血管紧张素ｅｎａｌａｐｒｉｌ和ｆｏｓｉｎｏｐｒｉｌ对ＳＨＲ心肌超微结构的逆转作用。方法：将１０月１８只ＳＨＲ随机分为Ｅｎａｌａｐｒｉｌ（ＳＨＲＥ）、Ｆｏｓｉｎｏｐｒｉｌ（ＳＨＲＦ）和生理盐水（ＳＨＲＣ）三组,给药剂量为１０ｍｇ／ｋｇ／ｄ腹脸内注射８周。测定血压、心室重量指数,电镜观察心肌超微结构改变。结果：两药物组心室肥厚均不同程度消退,部分逆转心肌超微结构改变,而且Ｆｏｓｉｎｏｐｒｉｌ     

抑制1-磷酸鞘氨醇裂解酶活性加重缺血性心力衰竭

目的:观察1-磷酸鞘氨醇(S1P)裂解酶(SPL)在小鼠缺血性心衰(HF)模型中的作用。方法:将60只成年雄性C57/BL6J小鼠随机分为以下4组:假手术(Sham)组、心肌梗死(MI)组、假手术+THI(Sham+THI)组[THI是SPL的抑制剂]及MI+THI组,每组15只(n=15),将25 mg/L THI溶于饮水中,于手术24 h后连续饲喂2周。MI4周后,采用ELISA试剂盒测定心肌中S1P的含量。根据心脏质量/体质量(HW/BW)评价心肌肥厚。用小动物心脏超声评估小鼠心脏结构和功能,经Masson三色染剂染色法观察心脏纤维化。用Western blot检测转化生长因子-β(TGF-β)蛋白的表达。实时PCR检测Ⅰ、Ⅲ型胶原、心房钠尿肽(ANP)、脑钠尿肽(BNP)和平滑肌肌动蛋白-α(α-SMA)mRNA的水平。结果:与MI组相比,MI+THI组小鼠心肌组织中S1P的含量增加(P0.01);左心室射血分数(LVEF)降低(P0.01),左心室收缩末期内径(LVESD)和舒张末期内径(LVEDD)均增加(均P0.05),HW/BW增加(P0.01),心脏纤维化加重;TGF-β蛋白的表达增加(P0.01);Ⅰ、Ⅲ型胶原、ANP、BNP和α-SMA mRNA的水平均显著增加(均P0.01)。与Sham组相比,Sham+THI组小鼠上述指标无显著差异。结论:抑制SPL的活性可能增加梗死后心肌病理性S1P信号的激活,加重MI后的心脏重构和HF。