运动对心血管系统内皮素的影响

采用文献资料研究法,分析了内皮素的产生及作用机制,探讨了运动对内皮素的影响,提出不同运动使内皮素发生不同改变,在运动过程中内皮素参与机体水、电解质平衡的调节及心脏的重塑.为心脏内分泌功能的研究提供新的思路和参考.     

Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor

Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.     

运动训练与内皮素

内皮素对人体具有广泛的生物学效应.简要介绍了内皮素的生物学功能,并从不同方式运动对内皮素分泌的影响、运动影响心血管系统内皮素分泌的机制及内皮素对运动时心血管系统的作用等几个方面进行综述.     

内皮素与妇产科疾病

为探讨内皮素含量的高低与某些妇产科疾病的关系，从内皮素的产生、分布及其与妇产科疾病的关系等方面进行了简要综述。     

运动对内皮素分泌影响的分析与研究

运动作为一种特殊刺激会引起机体内皮细胞分泌水平发生改变．该文总结人们研究的不同运动形式、不同运动强度及运动训练对内皮素分泌的影响，旨在促进运动对内皮素分泌的影响的研究，并为在运动训练中，探索合理的运动强度和运动时间，提高运动成绩，防止运动性疾病产生提供科学的依据。     

Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons

During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unknown. Here we demonstrate in mouse embryos that the endothelin family member Edn3 (ref. 1), acting through the endothelin receptor EdnrA (refs 2, 3), directs extension of axons of a subset of sympathetic neurons from the superior cervical ganglion to a preferred intermediate target, the external carotid artery, which serves as the gateway to select targets, including the salivary glands. These findings establish a previously unknown mechanism of axonal pathfinding involving vascular-derived endothelins, and have broad implications for endothelins as general mediators of axonal growth and guidance in the developing nervous system. Moreover, they suggest a model in which newborn sympathetic neurons distinguish and choose between distinct vascular trajectories to innervate their appropriate end organs.     

内皮素对心脏功能的影响

内皮素(Endothelin,ET)是由血管内皮细胞产生的具有强烈缩血管作用的血管活性肽.大量实验表明,内皮素对心脏具有广泛的影响,使冠状血管收缩,对心脏产生正性肌力作用,通过内皮素受体参与神经体液因素对心肌细胞的调节作用.     

EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF

Cross-communication between different signalling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. The transactivation of epidermal growth factor receptor (EGFR)-dependent signalling pathways upon stimulation of G-protein-coupled receptors (GPCRs), which are critical for the mitogenic activity of ligands such as lysophosphatidic acid, endothelin, thrombin, bombesin and carbachol, provides evidence for such an interconnected communication network. Here we show that EGFR transactivation upon GPCR stimulation involves proHB-EGF and a metalloproteinase activity that is rapidly induced upon GPCR-ligand interaction. We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals. The pathophysiological significance of this mechanism is demonstrated by inhibition of constitutive EGFR activity upon treatment of PC3 prostate carcinoma cells with the metalloproteinase inhibitor batimastat. Together, our results establish a new mechanistic concept for cross-communication among different signalling systems.     

ET_A受体拮抗剂杨梅酸A的半合成研究

合成了潜在的特定ETA受体拮抗剂杨梅酸A。合成方法是通过廉价易得的齐墩果酸为原料,通过3-OH Dess-Martin（DMP）氧化、臭氧化、液氨还原等11步反应,得到杨梅酸A,中间体及目标产物的结构通过^1H NMR、^13C NMR进行了表征。     

慢性肝病患者血浆内皮素含量与肝损害的关系研究

探讨血浆内皮素（ET）在慢性肝病患者中的变化规律以及与肝损害的关系。用放射免疫法测定110例慢性肝病患者及30例正常人血浆ET含量。结果表明，各种类型的慢性肝病患者血浆ET水平均显著高于正常组，且与临床类型有关。ET水平与谷丙转氨酶（ALT）及血清胆红素（SB）呈正相关，与白／球比例（A／G）和凝原酶原时间（PT）呈负相关，与甲胎球蛋白（AFP）无显著相关性。提示ET与肝病的慢性化程度及肝损害程度有关，可作为病情及预后判断的一项指标。     

Cloning and expression of a cDNA encoding an endothelin receptor

Endothelins are a newly described peptide family consisting of three peptides (ET-1, ET-2 and ET-3) which are the most potent vasoconstrictive peptides known. They are crucial in the regulation of vascular smooth muscle tone. The diverse functions of endothelins are thought to be mediated by interaction with many different receptors coupled to the inositol phosphate/calcium ion messenger pathway. However, because of the structural resemblance of the three peptides, the presence and nature of multiple endothelin receptors remain to be elucidated. We report here the cloning of a complementary DNA encoding a bovine endothelin receptor, which has a transmembrane topology similar to that of other G protein-coupled receptors and shows specific binding, with the highest selectivity to ET-1 in animal cells transfected with the cloned cDNA. This receptor messenger RNA is widely distributed in the central nervous system and peripheral tissues, particularly in the heart and lung. Our results support the view that there are other receptor subtypes.     

NO样舒张因子和内皮素在急性缺氧肺动脉高压中的作用

在大鼠急性缺氧肺动脉高压模型、离体灌流肺动脉环模型及培养的牛肺动脉内皮细胞探讨ＮＯ样舒张因子（ＮＯ－ＬＲＦ）和内皮素（ＥＴ）在急性缺氧肺动脉高压中的作用。结果发现：ＮＯ合成前体Ｌ－Ａｒｇ（２５０ｍｇ／ｋｇ，ｉｖ）可有效降低急性缺氧肺动脉高压的幅度；在内皮完整血管环加入ＮＯ合成抑制剂Ｌ－ＮＮＡ（１０－４ｍｏｌ／Ｌ）、ＮＯ合成前体Ｌ－Ａｒｇ（１０－２ｍｏｌ／Ｌ）分别升高（＋８０％，Ｐ＜０．０１）和降低（－３５％，Ｐ＜０．０５）缺氧肺动脉收缩幅度，给予硝酸甘油（１０－４ｍｏｌ／Ｌ）直接补充ＮＯ可降低缺氧肺动脉收缩幅度；此效应可被可溶性鸟苷酸环化酶抑制剂亚甲蓝部分逆转；内皮素抗血清或内皮素Ａ受体结抗剂ＢＱ１２３对急性缺氧肺动脉高压及缺氧肺动脉收缩没有明显影响；Ｎｏｒｔｈｅｒｎ印渍杂交技术显示缺氧使培养的牛肺动脉内皮细胞ＮＯ合成酶（ＮＯＳ）基因表达明显受抑乃至缺失．结果提示：缺氧时ＮＯＳ基因表达受抑及ＮＯ－ＬＲＦ合成释放降低可能是急性缺氧肺动脉高压的发生机制之一，内皮素不起主要作用．     

复杂性疾病血栓前状态指标变化的共性研究

为研究复杂性疾病患者在血栓前状态的共性并探讨其意义,采用流式细胞仪、ELASA法、放射免疫法、全自动血凝分析仪等技术方法,检测复杂性疾病患者血小板表面P-选择素(CD62p)的表达,血浆组织型纤溶酶原激活剂(t-PA)及血浆组织型纤溶酶原激活抑制剂(PAI-1)、血清内皮素(ET-1)及凝血4项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)。结果表明:与正常对照组比较,复杂性疾病组血小板表面CD62p的表达及血浆PAI-1水平明显升高(P<0.05);复杂性疾病组血浆t-PA的含量明显降低(P<0.05);与正常对照组比较,肿瘤组血清ET-1水平明显升高(P<0.05)。上述指标与疾病组间比较差异无显著性(P>0.05);与正常对照组比较,各疾病组APTT时间明显缩短(P<0.05);与正常对照组比较各疾病组血浆FIB浓度明显升高(P<0.05)。其中肿瘤组血浆FIB浓度的变化比其他3个疾病组更为明显;与正常对照组比较,肿瘤组、糖尿病组及高血压组PT时间明显缩短(P<0.05);APTT,PT,TT进行疾病组间比较差异无显著性(P>0.05)。由此得出结论:复杂性疾病患者血小板活化、凝血功能增强、纤溶功能减退,存在明显的血栓前状态。血栓前状态可能是贯穿于复杂性疾病发生、发展过程的共同病理生理机制之一。     

Urotensin Ⅱ increases endothelin production by vascular smooth muscle cells in rats

The aim of this study was to observe the effects of urotensin Ⅱ (UII) on production of endothelin (ET) in rat aortic vascular smooth muscle cells (VSMC). Cultured VSMCs incubated with various concentrations of UII were used to measure the VSMC 3H-TdR incorporation, the amount of ET mRNA and ET production in VSMCs. In this work we found that UII (10-10-10-8 mol/L) promoted VSMC 3H-TdR incorporation (47%-83%, P < 0.01) and increased the amount of ET mRNA by 17.1% (P < 0.05) to 112.8% (P < 0.01), respectively, in a concentration dependent manner compared with control. After 4 and 8 h incubation, 10-10-10-8 mol/L of UII elevated the ET synthesis and release in a concentration dependent manner. After 4 h incubation, the content of ET in medium was 4.9, 5.36 and 7.12 pg/mL (P < 0.01). After 8 h incubation, the ET content released from VSMCs was 12.6, 12.07 and 17.17 pg/mL (P < 0.01). In addition, it was found that BQ123, a specific ETA receptor antagonist, obviously decreased the VSMC DNA synthesis induced by UII. The results of this study showed that UII could stimulate the ET mRNA expression and ET production in VSMC. The effects of UII on VSMC DNA synthesis were partly mediated by ET autocrine pathway. It suggests that the interaction between UII and ET plays an important biological regulating role as endogenous active peptides.     

经皮肺动脉去交感神经冷冻消融术治疗犬肺动脉高压疗效评价

摘要:目的 通过野百合碱诱导的犬肺动脉高压模型,观察肺动脉去交感神经冷冻消融术后 6 个月的肺动脉平均压力( mPAP) 、肺毛细血管楔压( PCWP)及内皮素受体-1( ET-1)变化,评估冷冻消融去比格犬肺动脉交感神经的安全性和有效性。 方法 将 15 只比格犬随机分为 A 组(冷冻消融组) 、B 组(假手术组) 及 C 组( 对照组) ,对比观察比格犬手术前后 mPAP、PCWP 及 ET-1 水平变化。 结果 A、B 和 C 各组术后 6 个月,mPAP、PCWP 和 ET-1 值均低于术前水平,差异有统计学意义( P<0. 05) 。 结论 犬肺动脉高压经皮肺动脉去交感神经冷冻消融术安全且有效,术后表现出延续性降肺动脉压力效果。     

血府逐瘀汤对动脉粥样硬化大鼠血脂及血管活性物质的影响

通过观察血府逐瘀汤对动脉粥样硬化(atherosclerosis,AS)大鼠血脂及血管内皮活性因子的影响,探讨血府逐瘀汤抗动脉粥样硬化的机制.将40只SD大鼠随机分为对照组、模型组、治疗组(血脂康组、血府逐瘀汤高剂量组、血府逐瘀汤低剂量组).对照组给予正常饮食;模型组给予高脂饮食;治疗组在高脂饮食基础上分别给予血脂康,...     

柿叶黄酮的降血压作用及其作用机制研究

用一氧化氮合酶抑制剂N^G-硝基-L-精氨酸甲酯（N^G-nitro-L-arginine-methlester,L-NAME）复制高血压大鼠模型研究柿叶黄酮对高血压大鼠的降血压作用。试验分为正常对照组、模型对照组,柿叶黄酮低、中、高剂量组（20mg·kg^-1·d^-1,40mg·kg^-1·d^-1,80mg·kg^-1·d^-1）、卡托普利组（10mg·kg^-1·d^-1）。每周测大鼠尾动脉压,给药4周后处死大鼠,测定血清中一氧化氮（N0）、血浆内皮素（ET）和血管紧张素（Ang）Ⅱ的含量。结果显示,柿叶黄酮能明显降低L—NAME诱导的高血压大鼠的血压（P〈0．05）,并在剂量范围内呈剂量依赖性;与模型对照组相比,血清N0含量上升[（77．15±15．14）μmol·L^-1vs（30．77±10．62）μmol·L^-1,P〈0．01],血浆ET含量降低[（56．21±9．23）pg·ml^-1vs（87．28±11．75）pg·ml^-1,P〈0．01],血浆AngⅡ含量降低[（503．4±33．40）pg·ml^-1vs（666．62±33．45）pg·ml^-1,P〈0．01]。柿叶黄酮可能是通过增加内源性舒血管活性物质的释放和减少内源性收缩血管活性物质的释放来调节两者之间的平衡而发挥其抗高血压作用。     

低频电刺激对脏器中激素含量的影响

摘要: 目的探索低频电刺激对中国树鼩死亡后脏器中激素水平的影响。方法给予中国树鼩低频电刺激,分别于死亡后0 h、3 h、6 h、12 h、18 h、24 h、36 h 和72 h 取甲状腺、肝脏、脾脏,用放射免疫法测定内皮素( endothelin,ET) 、心钠素( atrial natriuretic factor,ANF) 、血栓素( thromboxane,TX) 水平; 剥取死后0 h 中国树鼩中脑腹侧背盖区( ventral tegmental area,VTA) 检测c-fos 表达。结果电刺激后,中国树鼩尸体脏器中内皮素、心钠素、血栓素水平比对照组显著升高,其含量随死亡后时间的延长而降低,且呈现一定的趋势; VTA c-fos 表达明显增强。结论低频电刺激能引起中国树鼩脏器中激素的合成、释放和脑组织c-fos 表达。     

Urotensin Ⅱ increases endothelin production by vascular smooth muscle cells in rats

The aim of this study was to observe the effects of urotensin Ⅱ (UII) on production of endothelin (ET) in rat aortic vascular smooth muscle cells (VSMC). Cultured VSMCs incubated with various concentrations of UII were used to measure the VSMC ³H-TdR incorporation, the amount of ET mRNA and ET production in VSMCs. In this work we found that UII (10^-10—10^-8 mol/L) promoted VSMC ³H-TdR incorporation (47%—83%, P < 0.01) and increased the amount of ET mRNA by 17.1% (P < 0.05) to 112.8% (P < 0.01), respectively, in a concentration dependent manner compared with control. After 4 and 8 h incubation, 10^-10—10^-8 mol/L of UII elevated the ET synthesis and release in a concentration dependent manner. After 4 h incubation, the content of ET in medium was 4.9, 5.36 and 7.12 pg/mL (P < 0.01). After 8 h incubation, the ET content released from VSMCs was 12.6, 12.07 and 17.17 pg/mL (P < 0.01). In addition, it was found that BQ₁₂₃, a specific ET_A receptor antagonist, obviously decreased the VSMC DNA synthesis induced by UII. The results of this study showed that UII could stimulate the ET mRNA expression and ET production in VSMC. The effects of UII on VSMC DNA synthesis were partly mediated by ET autocrine pathway. It suggests that the interaction between UII and ET plays an important biological regulating role as endogenous active peptides.     

维生素E和疏血通注射液联用对不稳定型心绞痛患者的影响

目的观察维生素E和疏血通注射液联用对不稳定型心绞痛(UAP)患者的疗效及其时血浆一氧化氮、内皮素的影响.方法将70例符合WHO不稳定型心绞痛诊断标准的患者随机分为两组,对照组30例,常规抗心绞痛治疗,实验组在对照组治疗基础上加用维生素E100mg,1次/d口服,疏血通注射液6mL加入5%葡萄糖注射液250 mL中静点,1次/d.测定治疗前及治疗1,2,3,4周时的NO,ET-1水平及4周时的心绞痛症状、心电图的变化情况.另测30例体检健康者的ET-l,NO水平作为阴性对照.结果冠心痛心绞痛患者与健康体检者比较NO水平降低,ET-1水平增高.实验组第3,4周时与对照组比较ET-1水平降低,NO水平增高.实验组治疗前后差异有显著性,对照组治疗前后无差异显著性.治疗4周后实验组总有效率明显优于对照组.结论维生素E和疏血通注射液联用,可明显改善不稳定型心绞痛患者的血管内皮功能,提高治疗效果.