STAR蛋白QKI在去甲肾上腺素诱导大鼠心肌肥厚时的表达变化

目的：探讨QKI mRNA及蛋白在SD大鼠病理性心肌肥厚时的表达。方法：采用去甲肾上腺素制备SD大鼠心肌肥厚模型，利用实时荧光定量PCR法和蛋白质免疫印迹法检测大鼠心肌肥厚时QKI mRNA和蛋白质的表达变化。结果：在SD大鼠心脏中有3种QKI异构体mRNA和QKI蛋白的表达；当去甲肾上腺素持续输注引起大鼠心肌肥厚时，心脏QKI-5 mRNA和QKI蛋白质表达水平均明显降低（P<0.05）；去甲肾上腺素诱导培养的乳鼠心肌细胞肥大时，QKI-5 mRNA表达量也明显低于对照（P<0.05）。结论：大鼠心脏有QKI mRNA和蛋白质表达，心脏病理性肥厚时其表达发生变化。     

血管紧张素转换酶抑制剂防治实验性心肌肥厚的形态学研究

目的：观察血管紧张素转换酶抑制剂卡托普利防治心肌肥厚的作用,并比较倍他乐克对心肌肥厚的影响。方法：选用腹主动脉缩窄的大鼠实验性心肌肥厚模型,分心肌肥厚组、卡托普利组、倍他乐克组和对照组。常规电镜制样,除定性观察外,每组分别进行了有关体视学分析。结果：心肌肥厚组心肌细胞超微结构病变明显,间质胶质纤维增多;卡托普利组心肌细胞和间质超微结构基本正常。心肌肥厚和倍他乐克的心肌肥厚原纤维体密密度低于卡托普利     

胚胎期缺氧后心肌内去甲肾上腺素的含量变化

本文研究了胚胎期缺氧后对新生鼠心肌内去甲肾上腺素(NA)含量的影响,发现缺氧组心肌内NA含量在早期都低于对照组,但心重与体重之比值却高于对照组,尤以5天组最显著,P<0.01。     

卡托普利对实验性腹主动脉狭窄大鼠左心室肥厚的影响

目的进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法采用实验性腹主动脉银夹狭窄大鼠模型,观察左心室重量指数（ＬＶＭＩ）,放免测定血浆血管紧张素Ⅱ（ＡｎｇⅢ）及左心室心肌局部 Ａｎｇ Ⅱ。结果模型组ＬＶＭＩ、血浆ＡｎｇⅡ、左心室心肌Ａｎｇ　Ⅱ水平明显高于假手术组;卡托普利组ＬＶＭＩ、血浆Ａｎｇ Ⅱ、左心室心肌Ａｎｇ　Ⅱ明显下降。结论使用腹主动脉银夹狭窄方法建立心脏后负荷增加的心肌肥厚动物模型是可靠的,卡托普利确有抗心肌肥厚的作用。     

卡托普利对实验性腹主动脉狭窄小鼠左心室肥厚的影响

目的 进一步证实实验性腹主动脉狭窄大鼠左心室肥厚及卡托普利的作用。方法 采用实验性腹主动脉银夹狭窄大鼠模型，观察左心室重量指数，放免测定血浆血管紧张素Ⅱ及左心室心肌局部ＡｎｇⅡ。结果 模型组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ水平明显高于假手术组；卡托普利组ＬＶＭＩ，血浆ＡｎｇⅡ，左心室心肌ＡｎｇⅡ，左心室明显下降。     

SHR心脏肥厚对心肌胶原及血浆紧张素Ⅱ含量的变化

采用病理学及放射免疫方法检测16、24和32周龄自发性高血压大鼠（SHR）心肌胶原容积分数（CVF）和心肌血管周围胶原面积（PVCA）、心脏肥厚指标及血浆和组织血管紧张素Ⅱ（AngⅡ）浓度,并以同龄Wister大鼠作对照,以探讨SHR心脏肥厚进展阶段心肌纤维化、心脏重构、血浆和组织血管紧张素Ⅱ浓度及其相互关系。结果显示,各组SHR收缩压明显增高、心脏肥厚指标心脏重量（HW）、左室重量（LVW）、左室重量指数（LVW／BW）显著增加,血浆、心肌组织AngⅡ浓度明显增高;24、32周龄SHR的CVF和PVCA显著增加;SHR心肌组织AngⅡ浓度与CVF呈显著正相关。结果表明心肌纤维化可能参与SHR代偿性心脏肥厚阶段心脏重构病理过程,组织AngⅡ可能是导致SHR代偿性心脏肥厚阶段心肌纤维化的重要机制之一。     

自发性高血压鼠心肌内去甲肾上腺素的变化

运用高效液相色谱电化学检测仪测定24只自发性高血压鼠(SHR)心肌内去甲肾上腺素(NA)的含量。SHR分成3个月与6个月龄两组,并与同龄组的正常血压京都种大白鼠(WKY)作比较。结果在3个月龄组的SHR心肌内NA含量低于WKY,而6个月龄组的SHR则高于WKY,两者都有显著性差异。同时亦测量了它们的血压变化。     

ILK在异丙肾上腺素诱导大鼠心肌肥厚组织中的表达

目的探讨心肌肥厚发生发展过程中ILK的表达特征。方法在大鼠背部皮下分别注射7、28和56 d异丙肾上腺素(ISO),判定心肌肥厚指标,利用免疫组织化学和免疫印迹技术,观察ILK在肥厚左心室肌中的表达。结果 ILK主要表达于心肌细胞胞膜和内皮细胞。与对照组相比,ISO组ILK阳性表达明显增强。随着造模时间的延长,肥厚心肌中ILK的表达含量逐渐升高。Western blot图像分析结果显示:ISO各实验组大鼠左心室心肌组织中的ILK蛋白表达带均强于对照组(P<0.01),7、28和56 d组间比较差异有统计学意义(P<0.05)。结论 ILK与心肌肥厚的发生和发展有关,心肌肥大越重,ILK含量增加越高。     

肥厚心肌胶原及基质金属蛋白酶的活性变化

探讨压力负荷增高性心肌肥厚时心肌胶原网络及心肌细胞外基质金属蛋白酶（ ＭＭＰｓ）活性的变化。腹主动 脉部分结扎术致大鼠压力负荷增高性心肌肥厚,ＶＧ染色和图像处理观察心肌胶原网络,酶谱法（Ｚｙｍｏｇｒａｐｈｙ）测定 心肌ＭＭＰｓ活性。结果：手术组大鼠术后２周即出现明显心肌肥厚,术后４周左室肥厚程度进一步加重。与假手术组 比较,左室心肌总胶原容积百分比（ＣＶＥ－Ｔ）于术后２周即增高（Ｐ＜０．０５）,术后４、８周大鼠ＣＶＦ－Ｔ和无小血管视野 ＣＶＦ（ＣＶＦ－ＮＶ）均明显增高（Ｐ＜０．０１）,手术组大鼠左室心肌组织ＭＭＰ－１活性明显低于相应假手术大鼠,但经胰蛋 白酶激活后其活性反而高于假手术大鼠。结论：压力负荷增高性心肌肥厚时伴有心肌胶原网络的重构,心肌组织内 ＭＭＰ－１活性调节异常可能与心肌胶原网络重构的形成有关。     

肾动脉狭窄对心肌内去甲肾上腺素的含量及血压的影响

本文研究了35只京都种大白鼠(WKY)肾动脉狭窄手术后对心肌内去甲肾上腺素(NA)含量及血压的影响,发现左肾动脉狭窄(2K1C)型与右肾切除后再作左肾动脉狭窄(1K1C)型心肌内NA含量在实验组都低于对照组,而血压则高于对照组,两者有统计学意义。实验组(或对照组)心肌内NA含量在2K1C型都高于1K1C型,两者有显著性差异,但血压则2K1C型低于1K1C型。     

心肌肥厚大鼠左室组织中肌醇磷脂途径特征

本研究观察了心肌肥厚大鼠左室组织中肌醇磷脂途径特征。对大鼠行腹主动脉部分缩窄术制作心肌肥厚模型 ,术后 10d处死动物测全心重 体重比值 ,以免疫印迹法测左室组织Gαq 11和PLC β3 蛋白含量 ,以放免法测左室组织 1,4,5 三磷酸肌醇 (IP3 )含量。结果显示术后 10d时腹主动脉部分缩窄 (CA)组大鼠全心重 体重比值明显高于假手术 (SO)组 (P <0 0 1) ,二组大鼠左室组织Gαq 11和PLC β3 蛋白含量无显著差异 ,CA组左室组织IP3 浓度明显高于SO组 (P <0 0 5 )。上述结果提示肌醇磷脂途径可能参与压力超负荷性心肌肥厚病理过程     

大鼠压力负荷型心肌肥厚相关基因片段分离和鉴定

本实验基于心甩肥厚过程中基因表达所发生的变化,采用ＣＤＮＡ差减杂交法分离其中存在表达差异的基因片段,在三个不同时期的六组材料中共分离出三十六修养异性基因片段,其中以心肌组织作为材料分离出二十四个片段,以灌流分离的心肌细胞作为材料的十二个片段。杂交结果显示它们在心肌肥厚组和对照组中确定存在表达差异 。     

肾上腺素能受体与心肌肥大的研究进展

心肌肥大是一种较缓慢而有力的代偿形式,然而它不是无限度的,心肌肥大最终将引起心室功能异常而导致心力衰竭,这往往是心血管疾病患者的主要死因之一。肾上腺素能受体(adrenergic receptor,AR)是介导儿茶酚胺作用的一类组织受体,研究表明AR与心肌肥大和心力衰竭的发生密切相关。因此,本文就几种AR与心肌肥大近年的研究进展进行综述,以便更好的了解心肌肥大的发生机理。     

Left ventricular hypertrophy improves cardiac performance in spontaneously hypertensive rats

Cardiac function was studied in spontaneously breathing, adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY). By rapid intravenous blood infusion, the relation between left ventricular end-diastolic pressure (LVEDP) and stroke volume (SV) was determined while the cardiac nervous control was pharmacologically blocked. Since SV is greatly influenced by the level of afterload (mean arterial pressure, MAP), SV was also determined at increased MAP (constriction of abdominal aorta) and at decreased MAP (vasodilation by hydralazine). At low LVEDP levels, a righward shift of the Frank-Starling relationship was observed in SHR. This rightward shift seems mainly to depend on the increased MAP present in SHR since it was less prominent if MAP was lowered to normotensive levels in SHR. Maximal SV during volume infusion was similar in SHR and WKY, despite a much higher MAP in SHR. When peak SV was instead compared at similar MAP levels for both (either at ‘normotensive’ or ‘hypertensive’ levels) it was always significantly greater in SHR, and was increased largely in proportion to their increased left ventricular weight. This indicates that the left ventricular hypertrophy present in SHR is, at least at this stage, a physiological adaptation of the heart to increase its performance, in order to maintain a normal SV and hence cardiac output, despite an increased arterial pressure.     

The assessment of cardiac hypertrophy at autopsy

The total weight of the normal adult human heart as well as that of each ventricle is proportional to body size. Body weight is superior to height as a predictor of total heart and isolated ventricular weights. Ventricular wall thickness is an insensitive means of assessing ventricular hypertrophy. Heart weight is a poor predictor of isolated right ventricular mass but a slightly better predictor of isolated left ventricular mass. The only method of determining the presence or absence of hypertrophy with confidence is to use the Fulton technique for isolated ventricular weights. The use of an arbitrary upper and lower limit, as currently used, for isolated ventricular weights obtained by Fulton's method may, however lead to errors in determining the presence or absence of ventricular hypertrophy.     

Prevalence and upper limit of cardiac hypertrophy in professional cyclists

The term athlete's heart refers to an increased left ventricular mass. Few studies have assessed the prevalence and normal upper limit of cardiac hypertrophy in highly trained cyclists and this was the aim of this study. A group of 40 professional road cyclists [mean age 26 (SD 3) years] who had participated in European competitions for 3–10 years, were evaluated at the beginning of the 1992–93 season. Evaluation included a clinical history and physical examination, one and two-dimensional echocardiography, 12-lead resting electrocardiogram and a graded exercise test. Determination of the left ventricular mass index (LVMI) was performed using Devereux's formula with correction for the body surface area. Systolic and diastolic blood pressure were measured at rest and at peak exercise. Of the group 23 cyclists (58%) presented a LVMI greater than 130 g · m^–2, 21 cyclists presented a diastolic ventricular thickness equal to or greater than 13 mm, with a superior limit of 19 mm; 3 cyclists presented asymmetrical septum hypertrophy; and the relationship between posterior wall and left ventricular diastolic radius was equal to or greater than 0.45 in 14 cases (35%). Electrocardiographic abnormalities of ST-T segment were seen in only 1 subject. No correlation was found between the degree of ventricular hypertrophy and arterial blood pressure. We concluded that these professional cyclists showed a high prevalence of cardiac hypertrophy (58%). The distribution of this hypertrophy was concentric in 20/33 and asymmetric in 3/23 of the subjects with left ventricular hypertrophy. The electrocardiograms were normal in 98% of the subjects.     

多胺在异丙肾上腺素所致大鼠心肌肥厚中的作用及意义

目的： 研究多胺、鸟氨酸脱羧酶(ODC)及精脒/精胺乙酰基转移酶（SSAT）在异丙肾上腺素所致大鼠心肌肥厚中的作用及机制。方法: 异丙肾上腺素（ISO）皮下注射复制大鼠心肌肥厚模型,应用反向高效液相色谱（RP-HPLC）、RT-PCR和Western blotting结合图像分析系统,分别检测ISO作用不同时点大鼠心肌组织多胺含量、ODC和SSAT mRNA和蛋白的表达。结果: 与对照组比较,心脏重量参数在ISO注射后7 d时显著增加,ISO注射后1 d时腐胺含量增加（P<0.05）,5 d、7 d时显著增加（P<0.01）;精脒含量在ISO注射后3 d时开始增加,ISO注射后7 d时增加显著（P<0.01）,精胺含量略有增多（P<0.05）,总多胺池显著增加。心肌组织ODC和SSAT的 mRNA表达在ISO注射后1 d时升高(P<0.05或P<0.01）,并持续在较高水平。心肌组织ODC和SSAT的蛋白表达分别在ISO注射后1 d和ISO注射后5 d时升高,ISO注射后7 d时显著升高（P<0.01）。结论: 大鼠心肌组织多胺含量增加和ODC、SSAT的表达增强可能参与ISO所致心肌肥厚的病理过程。     

Cinnamaldehyde attenuates pressure overload-induced cardiac hypertrophy

Background: Cinnamaldehyde is a major bioactive compound isolated from the leaves of Cinnamomum osmophloeum. Studies have demonstrated that cinnamaldehyde has anti-bacterial activity, anti-tumorigenic effect, immunomodulatory effect, anti-fungal activity, anti-oxidative effect, anti-inflammatory and anti-diabetic effect. It has been proven that Cinnamaldehyde improves ischemia/reperfusion injury of pre-treatment. However, little is known about the effect of cinnamaldehyde on cardiac hypertrophy. Methods: Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cinnamaldehyde premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at week 7 after starting cinnamaldehyde (8 weeks after surgery). The extent of cardiac hypertrophy was evaluated by pathological and molecular analyses of heart samples. Meanwhile, the effect of cinnamaldehyde on myocardial hypertrophy, fibrosis and dysfunction induced by AB was investigated, as was assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Results: Our data demonstrated that echocardiography and catheter-based measurements of hemodynamic parameters at week 7 revealed the amelioration of systolic and diastolic abnormalities by cinnamaldehyde intervention. Cardiac fibrosis in AB mice was also decreased by cinnamaldehyde. Moreover, the beneficial effect of cinnamaldehyde was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of extracellular signal-regulated kinase (ERK) signaling pathway, which was blocked by cinnamaldehyde. Conclusion: Cinnamaldehyde may be able to retard the progression of cardiac hypertrophy and fibrosis, probably via blocking ERK signaling pathway.     

二甲双胍对压力超负荷大鼠心肌肥厚的影响

目的:探讨二甲双胍(MET)对高血压大鼠心肌肥厚的影响及其机制。方法:制作腹主动脉缩窄(TAC)大鼠高血压心肌肥厚模型,术后1周随机分为5组(每组8只),灌胃给药8周:sham组:假手术,予蒸馏水2mL;TAC组:TAC大鼠,予蒸馏水2mL;MET组:TAC大鼠,予MET300mg·kg-1.d-1;MN组:TAC大鼠,同时给予MET300mg·kg-1.d-1和NG-硝基-L-精氨酸甲酯(L-NAME,NOS抑制剂)50mg·kg-1.d-1;NAME组:TAC大鼠,予L-NAME50mg·kg-1.d-1。处理8周后测定超声心动图、血流动力学、心肌组织学、心肌AMP激活的蛋白激酶(AMPK)及内皮型一氧化氮合酶(eNOS)的水平及活性。结果:处理8周后,TAC组大鼠左心室室壁厚度、心脏重量/体重(HW/BW)以及左心室心肌血管周围纤维化及心肌间质纤维化程度较sham组显著升高,给予MET300mg·kg-1.d-18周后,左心室肥厚及心肌纤维化显著减轻,心肌收缩及舒张功能改善(P0.05)。同时给予NOS抑制剂L-NAME则显著抑制MET上述效应。MET组大鼠左心室心肌p-AMPKαThr172和p-eNOSSer1177水平以及心肌及血清一氧化氮水平较TAC组显著升高。结论:长期给予MET治疗,显著抑制压力负荷高血压大鼠心肌肥厚及心肌纤维化程度,同时心功能改善。其机制可能与MET激活AMPK-eNOS信号通路有关。