大鼠实验性心肌肥厚与心肌5-羟色胺含量的相关性

观察大鼠发生心肌肥厚时心肌组织中 5 羟色胺 (5 HT)及血管紧张素 Ⅱ (Ang Ⅱ )含量的变化 ,探讨 5 HT ,Ang Ⅱ与心肌肥厚发生的关系 .采用腹主动脉缩窄法建立压力超负荷心肌肥厚模型 ;注射甲状腺素 (0 .4mg·kg- 1,ip ,每日 1次 ,连续 2～ 4周 )法建立体液性心肌肥厚模型 ;分别用荧光分光光度法和放射免疫分析法测定 5 HT及Ang Ⅱ含量 .分别于主动脉缩窄后 4 ,6,8周 ,注射甲状腺素 2 ,3,4周检测 ,结果显示心肌肥厚程度逐渐加重 ;心肌组织中 5 HT及Ang Ⅱ含量也逐渐增加 ,并且 5 HT含量增加与肥厚程度呈正相关 .结果提示 5 HT与心肌肥厚的形成有关 ,两者之间的相互关系尚待进一步研究 .     

水杉总黄酮抗实验性心肌肌厚作用的研究

目的 研究水杉总黄酮对实验性心肌肥厚的作用及其机制。方法 采用腹腔动－静脉造瘘建立大鼠容量超负荷心肌肥厚模型,水杉总黄酮灌胃给药,持续５ｗｋ后,测定心室肌细胞内Ｃａ＾２＋浓度,血浆和心肌ＡｎｇⅡ、心肌ＤＭＡ及ＳＯＤ。结果 水杉总黄酮剂地减轻大鼠心脏重量,抑制心室ＲＮＡ和蛋白质合成,降低心室肌内Ｃａ＾２＋浓度和心室ＲＮＡ和蛋白质合成,降低心室肌细胞内Ｃａ＾２＋浓度和心室ＡｎｇⅡ,ＭＤＡ含量,增加ＳＯ     

治疗心肌肥厚药物的进展

本文就近3年治疗心肌肥厚（特别是左室肥厚）的药物的研究进展作了综述,主要讨论了血管紧张素转换酶抑剂、血管紧张素Ⅱ受体Ⅰ阻断剂,钙拮抗剂、利尿剂等。对各类药物的治疗效果作出评价。并就心肌肥厚药物治疗的未来对策作了探讨。     

血管紧张素受体拮抗剂对心肌肥厚的防治作用

左室心肌肥厚是引起心血管疾病发生率与死亡率增高的危险因素之一。而血管紧张素Ⅱ（AngiotensinⅡ，AngⅡ）在心肌肥厚形成中起着重要的作用。AngⅡ受体拮抗剂通过选择性拮抗AngⅡ受体亚型AT1介导的生理效应而具有防治心肌肥厚的作用。本文就其在防治心肌肥厚可能的作用途径进行了综述。同时为寻找新的抗心肌肥厚药物提供了一些思路。     

坎地沙坦的抗高血压及对左室肥厚的逆转作用

目的观察坎地沙坦降压疗效及其对原发性高血压(EH)左室肥厚(LVH)的逆转作用。方法 83例患者口服坎地沙坦8mg,1次/d,治疗8周,用动态血压仪记录坎地沙坦治疗EH患者的降压效果,用超声心动图测量LVH患者的左心肥厚的改善情况。结果坎地沙坦可使24h血压平稳下降且左室质量指数较治疗前减低(P<0.01)。结论坎地沙坦能有效地控制血压的升高,对EH的LVH有逆转作用。     

钙蛋白酶在大鼠心肌肥厚中的作用及调节

目的 探讨压力超负荷下,钙蛋白酶参与心肌肥厚的信号转导机制.方法 16只SD大鼠随机均分为模型组和对照组.模型组采用不完全结扎腹主动脉法建立大鼠高血压心肌肥厚模型.放射免疫法检测两组心肌心房肽(ANF)、血管紧张素Ⅱ(AngⅡ)水平;Western blot法检测左室心肌钙蛋白酶的表达水平.结果 模型组术后血压、心肌ANF、AngⅡ含量、左室心肌钙蛋白酶同工酶u表达水平明显高于对照组(P＜0.01).结论 心肌肥厚组织中钙蛋白酶同工酶u表达增加,钙调神经磷酸酶信号通路参与了心肌肥厚的发病过程.     

洛沙坦抗高血压及左室肥厚的疗效观察

目的 :观察血管紧张素 受体拮抗剂—洛沙坦的降压效果及对高血压病合并左室肥厚的影响。方法 :4 6例合并左室肥厚的 期高血压病患者服用洛沙坦 5 0 mg/ d,观察其血压的变化及治疗前和 6个月后左室质量 (L VM)。结果 :用洛沙坦后 4 d～ 6d血压开始下降 ,2周血压趋向正常 ,4周血压继续缓慢下降 ,6周时达到最大降压效果。 L VM在 12周时无明显变化。 2 4周表现轻度 L VM减少。结论 :洛沙坦是抗高血压的一个有效治疗药物 ,对左心室肥厚有轻度逆转作用     

大鼠压力超负荷性心肌肥厚与氧自由基的关系

实验采用腹主动脉缩窄法复制大鼠心肌肥厚模型，观察心肌过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）水平以及尼群地平（Ｎｉｔ）和卡托普利（Ｃａｐ）治疗的作用。结果表明：大鼠腹主动脉缩窄后，左室重量增加，同时心肌匀浆中ＬＰＯ含量增高，ＳＯＤ活性下降，经相关关系分析，ＬＶＷ／ＢＷ与心肌组织ＬＰＯ含量显著正相关，ｒ为０．７６９，而与总ＳＯＤ活性呈显著性负相关，其ｒ为０．７８５。应用Ｎｉｔ、Ｃａｐ治疗能降低心肌组织中ＬＰＯ含量，升高ＳＯＤ活性，明显阻止心肌肥厚的形成。研究结果表明，氧自由基可能参与了心肌肥厚的发生和发展     

榅桲总黄酮对自发性高血压大鼠心肌肥厚的抑制作用及机制研究

目的研究榅桲总黄酮对自发性高血压大鼠心肌肥厚的抑制作用及可能的作用机制。方法自发性高血压大鼠分为模型组、卡托普利组(25μg·g~(-1))、杜仲平压片组(30μg·g~(-1))、榅桲总黄酮低(40μg·g~(-1))、中(80μg·g~(-1))、高剂量组(160μg·g~(-1)),WKY大鼠为正常对照组。给药16周后进行心脏组织病理学检查,评价靶器官损伤程度,测定血或心脏组织中血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、醛固酮(aldosterone,ALD)水平,并分别通过RT-PCR和Western blot检测心肌组织ACE、ACE2和AT_1的mRNA和蛋白表达水平,评价榅桲总黄酮对RAAS系统的影响。结果与SHR组相比,榅桲总黄酮中剂量组(SHR+COMF-M)和高剂量组(SHR+COMF-H)心脏质量(HW)、心脏质量/体质量(HW/BW)、左室质量(LVM)、左室质量/体质量(LVM/BW)均有不同程度减小,榅桲总黄酮可抑制SHR心肌细胞肥大,使心脏和血液中的AngⅡ和ALD含量减少(P<0.01或P<0.05)。与SHR组相比较,榅桲总黄酮各剂量组心肌组织血管紧张素转化酶(angiotensin-converting enzyme,ACE)和血管紧张素受体1(angiotensin receptor 1,AT_1)的mRNA和蛋白相对表达量有不同程度减少,ACE2的mRNA和蛋白相对表达量有不同程度增加(P<0.01或P<0.05)。结论榅桲总黄酮可抑制自发性高血压大鼠心肌肥厚,主要作用机制可能与抑制肾素-血管紧张素-醛固酮系统有关。     

牛磺酸对肾血管性高血压大鼠左室肥厚的保护作用

目的　观察牛磺酸 (Tau)对肾血管性高血压大鼠左室肥厚的影响 ,并探讨其机制。方法　建立二肾一夹 (2K1C)肾动脉狭窄性高血压模型。羟脯氨酸法测定大鼠心肌胶原含量 (MCC) ;放免法测定心肌AngⅡ (MAC)及Ald(MDC) ;原位杂交方法检测c fosmRNA表达 ;显微镜观察心肌组织结构改变并测量心肌纤维直径 (MFD) ,并进行线性相关分析。结果　 2K1C组大鼠MCC、MAC、MDC含量及MFD较Sham组增加 (P <0 0 1) ,c fosmRNA表达高于Sham组 (P<0 0 1) ;心肌冠状动脉周围胶原纤维大量增生并向周围间质延伸 ;相关分析显示MCC及MFD皆与MAC、MDC正相关 (P <0 0 1)。牛磺酸 (5 0mg·kg-1·d-1)治疗 8wk降低2K1C大鼠尾动脉收缩压 (SBP)、MAC、MDF及MCC(P <0 0 1) ,左心室 /体重比 (LVWI)、MDC及心室肌c fosmRNA表达量亦明显下降 (P <0 0 1) ,并抑制心肌冠脉周围胶原纤维增生。结论　牛磺酸可通过降低心肌局部RAAS活性及c fosmRNA表达 ,从而抑制心肌细胞肥大及胶原纤维增生 ,有效防治肾血管性高血压左室肥厚。     

氯沙坦对血管紧张素Ⅱ诱导的心肌细胞核酸、蛋白质及c-fos基因表达抑制作用的研究

目的　观察氯沙坦（ｌｏｓａｒｔａｎ,ＬＴ）对血管紧张素Ⅱ诱导的心肌细胞核酸、蛋白质及ｃ ｆｏｓ基因表达的抑制作用。方法　应用培养乳鼠心肌细胞,观察血管紧张素Ⅱ亚型受体拮抗剂 ＬＴ对血管紧张素Ⅱ（ＡｎｇⅡ）诱导的心肌细胞肥大的抑制作用。结果　ＬＴ２×１０－６ｍｏｌ·Ｌ－１能明显抑制ＡｎｇⅡ对心肌细胞核酸及蛋白质合成的促进作用及ｃ ｆｏｓｍＲＮＡ表达。结论　心肌细胞膜表面的ＡＴ受体亚型介导了ＡｎｇⅡ促心肌细胞肥大作用。ｃ ｆｏｓ基因激活是ＡｎｇⅡ诱导心肌细胞肥大的重要机制之一。ＬＴ从受体水平阻断了ＡｎｇⅡ的作用,此类药物应是更具选择性的肾素 血管紧张素系统拮抗剂。     

水杉总黄酮对麻醉犬实验性心肌梗死的保护作用

目的　观察水杉总黄酮对麻醉犬急性心肌梗死的保护作用。方法　采用结扎犬冠状动脉左前降支的方法造成急性心肌梗死模型 ,十二指肠给药 ,测定犬冠脉循环及心肌耗氧量参数 ,心肌缺血程度和缺血范围 ,梗死面积 ,血清CK、LDH活性及FFA含量。结果　水杉总黄酮能降低冠脉阻力 ,增加冠脉流量 ,减少心肌耗氧量 ,减轻心肌缺血程度和缺血范围 ,缩小心肌梗死面积 ,降低血清CK、LDH活性及FFA含量。结论　水杉总黄酮能改善冠脉循环 ,减少心肌耗氧量 ,纠正心肌缺血时FFA代谢紊乱 ,对缺血心肌具有明显保护作用。     

Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats

1. Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2. In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3. In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4. Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5. We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo.     

卡托普利对培养乳鼠心肌细胞蛋白质合成的抑制作用

以培养乳鼠心肌细胞作为模型，观察了卡托普利对心肌细胞生长的抑制作风结果表明。卡托普利２０和２００ｕｍｏｌ·Ｌ￣（－１）作用于细胞７２ｈ，心肌细胞的总蛋白质量分别减少９％和１８％。但细胞数目未见明显变化。用［￣３Ｈ］亮氨酸结合的方法，测得血管紧张素Ⅱ１，１０．１００ｎｍｏｌ·Ｌ￣（－１）在４８ｈ内增加蛋白质合成２９％。５３％和７０％，但用［￣３Ｈ］胸腺嘧啶核苷结合的方法测得ＤＮＡ的合成未见明显增加。无论１００ｎｍｏｌ·Ｌ￣（－１）血管紧张素Ⅱ是否存在，卡托普利２０和２００ｕｍｏｌ·Ｌ￣（－１）均能够减少细胞的蛋白质合成。结果提示卡托普利可以直接抑制心肌细胞的生长。此作用可能与其抑制心肌肥厚有关。     

Effects of trans-resveratrol on hypertension-induced cardiac hypertrophy using the partially nephrectomized rat model

trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the cardiovascular system in a number of studies. It is, however, unclear whether this naturally occurring compound can protect against cardiac hypertrophy. The aim of the present study was to investigate the effects of resveratrol on cardiac hypertrophy in vivo and the potential underlying mechanisms involving endothelin (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague-Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation controls were simultaneously established in the present study. The systolic blood pressure (SBP) of rats was measured at baseline and, along with heart weight, after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined. In the present study, it was shown that, compared with rats in the sham-operated group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg), heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7 +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/- 26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO concentration had increased to 40.1 +/- 14.6 micromol/L. These values were significantly different from those obtained for the PNX group. In conclusion, trans-resveratrol appears to be able to protect against the increase in SBP and subsequent cardiac hypertrophy in vivo and the mechanisms responsible may involve, at least in part, modulation of NO, AngII and ET-1 production.     

高糖对去甲肾上腺素诱导的心肌细胞肥大的促进作用

目的　利用体外培养的乳鼠心肌细胞 ,观测高浓度葡萄糖对去甲肾上腺素诱导的心肌细胞肥大的影响 ,根据所得结果来推测高糖与心肌细胞肥大之间的相互关系及可能作用机制。方法　以培养的乳鼠心肌细胞为模型分组给药后 ,用Lowrys法测心肌细胞的蛋白质含量 ;用消化分离法 ,利用计算机图像分析系统测心肌细胞的体积 ;用 [3 H]leucine标记法测定心肌细胞蛋白的合成。结果　与对照组相比 ,高糖组心肌细胞蛋白含量、体积、蛋白合成均有明显增加 ,NE组心肌细胞蛋白含量、体积、蛋白合成增加更为明显 ;而与高糖组或NE组相比较 ,高糖加NE组心肌细胞蛋白含量、体积、蛋白合成增加则最为显著。结论　单纯高糖培养可明显促进心肌细胞肥大 ,同时高浓度葡萄糖可在去甲肾上腺素诱导的心肌细胞肥大的基础上促使其进一步肥大 ,且两者间作用效果具有不完全叠加性     

Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling

1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. Angiotensin AT1 receptor antagonism has been considered as a specific approach to block the renin-angiotensin system and been demonstrated to be able to prevent or regress LVH by interfering with the remodelling process of the heart. 2. Angiotensin AT1 receptor blockade induces a marked increase in angiotensin (Ang) II, which may stimulate the AT2 receptors. Gene expression of AT1 and AT2 receptors increases in a time-dependent manner in cardiac remodelling following myocardial infarction. 3. Considerable efforts have been made to clarify the role of AT2 receptors in cardiac hypertrophy and remodelling since the mid-1990s, resulting in controversial reports: the AT2 receptor mediates actions either opposite to or in coordination with those of the AT1 receptor. Moreover, there are many reports of no significant effects mediated by AT2 receptors. 4. Based on the studies reviewed in the present article, we assume that the predominant effect of AngII in cardiac hypertrophy and cardiac remodelling is growth promoting and that this effect is mediated mainly via AT1 receptors. The AT2 receptors may affect the hypertrophic process by interacting with other cardiac membrane proteins, enzymes and autacoids. Before coming to a conclusion as to whether AT2 receptor stimulation or antagonism is beneficial to the heart, more studies should be performed in different LVH models, especially long-term treatment protocols in vivo.     

Cardioprotective effects of granulocyte colony-stimulating factor in angiotensin II-induced cardiac remodelling

1. Granulocyte colony stimulating factor (G-CSF) is reported to have a beneficial effect on cardiac dysfunction in postinfarction and doxorubicin-induced cardiomyopathy. Thus, the aim of the present study was to investigate the effects of G-CSF on cardiac remodelling in angiotensin (Ang) II-induced hypertrophy. 2. Four groups of mice were investigated. The first group served as a control group. The second group was injected with recombinant human G-CSF (10 microg/kg per day, s.c.) on the first 5 days of each week and treatment was continued for 4 weeks. An osmotic minipump was implanted subcutaneously into each mouse in the third group so that pressor doses of AngII (2.88 mg/kg per day) or saline could be administered over a period of 4 weeks. The fourth group was infused with AngII (2.88 mg/kg per day) and injected with G-CSF (10 microg/kg per day, s.c.) for 4 weeks. 3. Angiotensin II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in mice. Treatment of mice with G-CSF did not reduce the AngII-induced increase in blood pressure, but ameliorated the development of cardiac fibrosis and hypertrophy. Infusion of AngII induced upregulation of angiotensin-converting enzyme (ACE) expression and downregulation of ACE2 expression. Treatment with G-CSF reduced cardiac levels of ACE and increased ACE2 expression. In addition, G-CSF treatment reduced the expression of osteopontin (OPN) and phospho-p70S6 kinase, which were upregulated by AngII infusion. 4. These results suggest that G-CSF reduces AngII-induced hypertrophy. Modulation of the expression of the ACE isoforms contributes to regression of AngII-induced cardiac hypertrophy. The effect of G-CSF to prevent cardiac fibrosis and hypertrophy may be mediated, in part, via inhibition of OPN expression and p70S6 kinase phosphorylation.     

淫羊藿总黄酮对实验性脑缺血的保护作用初探

目的观察淫羊藿总黄酮对大鼠局灶性脑缺血的保护作用。方法采用线栓法复制大鼠大脑中动脉栓塞模型（MCAO）,观察淫羊藿总黄酮对模型大鼠的作用。结果淫羊藿总黄酮降低MCAO模型大鼠的神经功能评分,降低脑组织含水量,增加SOD、NOS活性,降低MDA含量。结论淫羊藿总黄酮对实验性脑缺血模型有保护作用。