阻断血管内皮细胞乙酰胆碱靶标功能对血管内皮细胞结构和功能的影响

目的：研究阻断血管内皮细胞乙酰胆碱靶标(ETA)功能对血管内皮细胞结构和功能的影响。方法：以山莨菪碱为工具药，喂食兔3mon后急性处死，剖腹取主动脉，HE及ET VG染色光镜观察主动脉的组织学改变，电镜观察血管内皮细胞的超微结构改变。同时取胸主动脉、肺动脉、颈动脉、肾动脉和股动脉，进行离体血管功能实验。结果：生理状态下，长期给予兔山莨菪碱，血管内皮细胞结构受损，光镜下可见内皮细胞垂直附着在内弹力板上，电镜下可见内皮细胞呈网眼状损伤，有些内皮细胞即将脱落，线粒体肿胀。离体血管环实验研究发现ETA介导的内皮依赖性血管舒张反应显减弱。结论：生理状态下，反复阻断ETA，可使内皮细胞结构和功能受损，提示ETA具有内皮保护作用。     

胰岛素对心血管系统的作用

胰岛素通过刺激内皮细胞一氧化氮的合成发挥其对血管的重要调节作用。胰岛素对心血管系统的作用在联系胰岛素的代谢和心血管稳态方面具有重要作用。糖尿病、肥胖、血脂异常．高血压、冠心病以及动脉粥样硬化均具有血管内皮细胞功能紊乱。胰岛素抵抗可使血管内皮细胞的磷脂酰肌醇-3-激酶依赖性的胰岛素信号通路受损，进而促进胰岛素抵抗和内皮细胞功能紊乱之间的相互关系。应选择以减低胰岛素抵抗和改善血管内皮细胞功能为靶点的治疗．包括药物和生活方式干预。     

microRNA对子痫前期母体血管内皮细胞损伤作用的研究进展

子痫前期是威胁母婴健康的妊娠期常见疾病，孕妇常出现高血压、蛋白尿，伴或不伴其他脏器损伤。子痫前期发病机制较为复杂，母体血管内皮细胞受损和功能紊乱是子痫前期发病的重要环节，而子痫前期母体血管内皮细胞损伤的分子机制仍未完全阐明，临床亦缺乏较为有效的治疗方法。microRNA(miRNA)是一类对基因具有调控作用的非编码微小RNA,可通过修饰信号转导途径中的核心元件调控血管内皮细胞功能。有研究报道了miRNA与子痫前期母体血管内皮细胞血管收缩/舒张因子生成失衡、炎症反应、氧化应激、凋亡及血管生成障碍的关联性；且miRNA参与了子痫前期母体血管内皮祖细胞的增殖、迁移及分化功能。本文就miRNA在子痫前期母体血管内皮细胞损伤过程中的作用及可能机制作一综述，为今后子痫前期的诊治提供新思路。     

血管内皮细胞功能障碍与原发性高血压

血管内皮细胞功能障碍与原发性高血压密切相关。一方面血管内皮细胞功能障碍在原发性高血压的发生、发展过程中起重要作用;另一方面原发性高血压本身又加重血管内皮细胞功能障碍,形成恶性循环。现综述血管内皮细胞的生理功能、血管内皮细胞功能障碍与原发性高血压关系、血管内皮细胞损伤的检测及在高血压治疗中改善内皮细胞功能的思路。     

VEGF与白血病关系的研究进展

血管内皮生长因子是主要作用于血管内皮细胞的一种细胞因子，具有促进内皮细胞增殖、分化，增加微血管通透性及诱导血管生成等功能。血管内皮生长因子与白血病的关系亦受到国外学者的广泛关注。本文就VEGF与白血病的研究进展作一综述。     

内皮细胞生长抑制素的研究现状

从内皮细胞生长抑制素的来源、结构、药理作用、作用机制、制备方法、应用研究等诸方面，综述其最新研究进展。内皮细胞生长抑制素可通过阻断血管内皮细胞的生长及新生血管的形成，抑制肿瘤的生长和转移，成为目前抗肿瘤药物的研究热点。     

血管内皮功能障碍与急性冠状动脉综合征的相关研究

急性冠状动脉综合征(acute coronary syndrome,ACS)是一组危重的心血管疾病[1],其发病机制是冠状动脉粥样斑块破裂后继发血栓形成,与内皮细胞的功能和血小板的活化密切相关.正常情况下,血管内皮细胞是一种选择通透膜,是血液与组织的一道天然屏障.它具有感受器及效应器功能,同时血管内皮细胞是人体最大、功能活跃的代谢内分泌器官,产生和分泌多种生物活性物质,对血管的张力、生长、脂蛋白的代谢等方面起着调控作用,这些活性物质在局部作用于血管发挥其各自的生物学效应.目前临床上与血管内皮功能相关因子及影响因素在ACS等疾病中出现异常改变.     

中医药对糖尿病血管内皮细胞影响的研究进展

糖尿病（DM）血管病变一直是DM患者早死及致残的首要原因，多种因素参与了这一病理过程，其中血管内皮细胞（endothelial cell，EC）功能异常在其中扮演了至关重要的角色。近年来中医药在保护血管EC、防治和减轻DM发生发展过程中所造成的血管EC损伤方面有许多研究。     

调节与维护血管内皮细胞功能的药物

血管内皮细胞在抗动脉粥样硬化、抗血栓、溶血栓和舒张血管方面具有重要作用.应用抗氧化药物可以保护内皮细胞功能.药物调节内皮细胞功能的新途径是生物力药理学,即用药物调控生物力使其维持适宜水平,从而维护内皮细胞的正常功能和健康的血循环.     

高血压患者血管内皮细胞功能变化及降压治疗的逆转作用

目的 观察高血压患者血管内皮细胞功能变化及降压治疗对其逆转作用。方法 测定正常血压对照组及高血压患者钙通道阻滞剂氨氯地平（AM）和利尿剂吲达帕胺（IN）治疗前后的血浆内皮素（ET）、一氧化氮（NO）浓度。结果 高血压患者血ET增加，NO减少，NO/ET比值下降，结论 高血压患者血管内皮细胞功能紊乱越明显。其靶器官损害也越重。6周降压治疗可逆转内皮细胞功能，AM保护内皮细胞功能作用优于IN。     

Ectopic ATP synthase in endothelial cells: a novel cardiovascular therapeutic target

Adenosine triphosphate (ATP) synthase produces ATP in cells and is found on the inner membrane of mitochondria or the cell plasma membrane (ectopic ATP synthase). Here, we summarize the functions of ectopic ATP synthase in vascular endothelial cells (ECs). Ectopic ATP synthase is involved in adenosine metabolism on the cell surface through its ATP generation or hydrolysis activity. The ATP/ADP generated by the enzyme on the plasma membrane can bind to P2X/P2Y receptors and activate the related signalling pathways to regulate endothelial function. The β-chain of ectopic ATP synthase on the EC surface can recruit inflammatory cells and activate cytotoxic activity to damage ECs and induce vascular inflammation. Angiostatin and other angiogenesis inhibitors can have anti-angiogenic functions by inhibiting ectopic ATP synthase on ECs. Moreover, ectopic ATP synthase on ECs is a receptor for apoA-I, the acceptor of cholesterol efflux, which implies that endothelial ectopic ATP synthase is involved in cholesterol metabolism. Coupling factor 6 (CF6), a part of ectopic ATP synthase, is released from ECs and can inhibit prostacyclin synthesis and promote nitric oxide (NO) degradation to enhance NO bioactivity. Because ATP/ADP generated by ectopic ATP synthase can induce NO production, substances such as CF6 can inhibit NO generation by inhibiting surface ATP/ADP production. Thus, the components of ectopic ATP synthase are associated with regulation of vascular tone. Through these functions, ectopic ATP synthase on ECs is considered a potential and novel therapeutic target for atherosclerosis, hypertension and lipid disorders.     

New molecular mechanisms for cardiovascular disease:blood flow sensing mechanism in vascular endothelial cells

Endothelial cells (ECs) lining blood vessels have a variety of functions and play a critical role in the homeostasis of the circulatory system. It has become clear that biomechanical forces generated by blood flow regulate EC functions. ECs are in direct contact with blood flow and exposed to shear stress, a frictional force generated by flowing blood. A number of recent studies have revealed that ECs recognize changes in shear stress and transmit signals to the interior of the cell, which leads to cell responses that involve changes in cell morphology, cell function, and gene expression. These EC responses to shear stress are thought to play important roles in blood flow-dependent phenomena such as vascular tone control, angiogenesis, vascular remodeling, and atherogenesis. Much research has been done on shear stress sensing and signal transduction, and their molecular mechanisms are gradually becoming understood. However, much remains uncertain, and many candidates have been proposed for shear stress sensors. More extensive studies of vascular mechanobiology should increase our understanding of the molecular basis of the blood flow-mediated control of vascular functions.     

慢性支气管炎与肺气肿大鼠肺血管内皮细胞损伤的实验研究

目的研究慢性支气管炎（chronicbronchitis,CB）与肺气肿大鼠肺腺泡内肌型动脉（muscular artery,MA）内皮细胞（en-dothelialcell,ECs）损伤特点及红霉素（erythromycin,EM）的干预作用。方法 18只Wistar大鼠按随机数字表法分成3组：每组6只,正常对照组（A组）,CB与肺气肿组（B组）,EM治疗组（C组）。用气管内注入脂多糖（lipopolysaccharide,LPS）及烟熏方法制作CB与肺气肿模型。8周后在电镜下观察肺腺泡内MA的ECs结构变化,光镜下观察肺腺泡内MA重塑改变。结果 （1）肺腺泡内MA的EC结构变化：与A组比较,B组肺腺泡内MA的EC变性肿大甚至坏死,胞浆内大量空泡,线粒体肿胀、数目减少。核突起、核异质增多。C组以上改变明显改善。（2）肺腺泡内MA图像分析：以内膜面积/血管总面积（%）描述,A组为21±4,B组为37±3,C组为30±1,三组间比较差异有统计学意义（P均〈0.01）。结论 （1）CB与肺气肿大鼠存在肺血管EC损伤。（2）肺血管EC损伤是CB与肺气肿大鼠肺血管重塑的重要病理基础。（3）EM对CB与肺气肿大鼠肺血管EC损伤及肺血管重塑有一定保护作用。     

Propyl gallate inhibits the growth of calf pulmonary arterial endothelial cells via glutathione depletion

Propyl gallate (PG) as a synthetic antioxidant exerts a variety of effects on tissue and cell functions. Here, we evaluated the effects of PG on the growth and death of endothelial cells (ECs), especially calf pulmonary artery endothelial cells (CPAEC) in relation to reactive oxygen species (ROS) and glutathione (GSH). PG dose-dependently inhibited the growth of CPAEC and human umbilical vein endothelial cells (HUVEC) at 24 h. PG induced cell death in CPAEC, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ_m). PG generally increased ROS level in CPAEC but not in HUVEC. PG also dose-dependently increased GSH depleted cells in both ECs. The treatment with antioxidant of N-acetyl-cysteine (NAC) or ascorbate acid (AA) prevented CPAEC growth inhibition and death by PG, which was accompanied by the attenuation of GSH depletion but not by the reduction of ROS level. In conclusion, PG induced growth inhibition and death of ECs, especially CPAEC via GSH depletion.     

紫杉醇对兔血管内皮和平滑肌细胞增生影响的差异及意义

目的探讨紫杉醇对兔血管内皮和平滑肌增生影响的差异及意义.方法将兔血管平滑肌细胞接种于共培养体系上室、内皮细胞接种于下室建立体外内膜修复模型,观察紫杉醇对兔血管平滑肌和内皮细胞3H-TdR掺入、细胞计数和迁移率的影响,用直线回归法计算紫杉醇对平滑肌和内皮细胞增生迁移的半数有效抑制浓度IC50.结果在1 nmol·L-1～1 μmol·L-1之间,紫杉醇呈浓度依赖地抑制平滑肌细胞3H-TdR掺入、细胞计数和迁移(n=6, P＜0.01).在10 nmol·L-1～1 μmol·L-1之间,紫杉醇呈浓度依赖地抑制内皮细胞3H-TdR掺入、细胞计数和迁移(n=6, P＜0.01).1 nmol·L-1紫杉醇对内皮细胞3H-TdR掺入和细胞计数有抑制倾向,但与对照组相比无统计学差异.而1 nmol·L-1的紫杉醇却已显著抑制内皮细胞迁移(n=6, P＜0.01).紫杉醇对兔血管平滑肌细胞增生、迁移抑制的IC50分别为 10.09±0.47、9.16±0.54 nmol·L-1,对内皮细胞增生、迁移抑制的IC50分别为 19.05±0.35、5.37±0.51 nmol·L-1.10 nmol·L-1紫杉醇作用 20 min 在观察时间内能持续抑制融合内皮组平滑肌增生,而对数内皮组平滑肌增殖在10 d时明显高于对照组.结论紫杉醇在抑制兔血管平滑肌细胞增生的同时也抑制内皮增生,紫杉醇干预后平滑肌细胞增生延迟与内皮细胞再生延迟密切相关.     

Emerging roles of long non‐coding RNAs in the toxicology of environmental chemicals

Environmental chemicals (ECs) are drawing great attention to their effects on health and their toxicological mechanisms are being investigated. Long non‐coding RNA (lncRNA) is a class of RNA with more than 200 nucleotides and does not have protein coding potential. Recently, it is emerging as a star molecule that participates in a wide range of physiological and pathological processes. It has been reported to be abnormally expressed in diseases. As an epigenetic factor, lncRNAs play an important role in the response of organisms to environmental stress. Their roles in the toxicity of ECs are being identified. Altered expression profiles of lncRNAs have been explored after exposure to ECs. Various kinds of ECs are reported to disturb the expression of lncRNAs in vitro and in vivo. Then, dysregulated lncRNAs can affect the expression of target genes directly or indirectly via regulating the level of microRNAs. The network among lncRNAs, microRNAs and mRNAs can initiate or impede specific signaling pathway and lead to adverse outcome upon exposure to ECs. Recovery of the lncRNAs level by overexpression or knockdown technology diminished the effect induced by ECs. In the review, biological roles of lncRNAs are depicted. The lncRNAs involved in the toxicology are summarized. Types of ECs that have been reported to affect the expression of lncRNAs are categorized. The interaction between various types of ECs and lncRNAs is discussed.     

同型半胱氨酸对大鼠主动脉内皮细胞脂质过氧化的影响

目的：探讨同型半胱氨酸（ＨＣＹ）对大鼠主动脉内皮细胞（ＥＣ）脂质过氧化的影响。方法：取体重１５０～２００ｇ健康雄性Ｗｉｓｔａｒ大鼠胸主动脉,以组织贴块法进行ＥＣ培养,第５代用于实验,各实验组及对照组均为６孔细胞,实验组加入５ｍｍｏｌ／ＬＨＣＹ或５ｍｍｏｌ／ＬＨＣＹ＋２５μｍｏｌ／ＬＣｕ＾２＋对照组不加ＨＣＹ。分别在不同时限观察细胞形态并测定丙二醛（ＭＤ）浓度,超氧化物歧化酶（ＳＯＤ）活性和乳酸脱氢     

Alkylphospholipids inhibit capillary-like endothelial tube formation in vitro: antiangiogenic properties of a new class of antitumor agents

Synthetic alkylphospholipids (APLs), such as edelfosine, miltefosine and perifosine, constitute a new class of antineoplastic compounds with various clinical applications. Here we have evaluated the antiangiogenic properties of APLs. The sensitivity of three types of vascular endothelial cells (ECs) (bovine aortic ECs, human umbilical vein ECs and human microvascular ECs) to APL-induced apoptosis was dependent on the proliferative status of these cells and correlated with the cellular drug incorporation. Although confluent, nondividing ECs failed to undergo apoptosis, proliferating ECs showed a 3-4-fold higher uptake and significant levels of apoptosis after APL treatment. These findings raised the question of whether APLs interfere with new blood vessel formation. To test the antiangiogenic properties in vitro, we studied the effect of APLs using two different experimental models. The first one tested the ability of human microvascular ECs to invade a three-dimensional human fibrin matrix and form capillary-like tubular networks. In the second model, bovine aortic ECs were grown in a collagen gel sandwich to allow tube formation. We found that all three APLs interfered with endothelial tube formation in a dose-dependent manner, with a more than 50% reduction at 25 micromol/l. Interference with the angiogenic process represents a novel mode of action of APLs and might significantly contribute to the antitumor effect of these compounds.     

Regulation of endothelin-1 production in cultured rat vascular smooth muscle cells

Endothelin-1 (ET-1) is secreted from all rat vascular smooth muscle cells (VSMCs) examined, in addition to endothelial cells (ECs). An average secretion rate of ET-1 from rat VSMCs was determined to be 10% that excreted from ECs. We examined the effects of 22 substances on ET-1 secretion from VSMCs and compared them with those from ECs. Transforming growth factor-beta1 (TGF-beta), acidic and basic fibroblast growth factors, epidermal growth factor, angiotensin II, and adrenaline stimulated ET-1 secretion from VSMCs, whereas forskolin, thrombin, and platelet-derived growth factor-BB reduced it. Only TGF-beta and phorbol ester elicited consistent effects on ET-1 secretion from VSMCs and ECs. Regulation of ET-1 and adrenomedullin secretion from VSMCs was distinctly different. These data suggest that ET- 1 production in VSMCs is regulated by a mechanism separate from that in ECs and from adrenomedullin production in VSMCs. Chromatographic analysis showed immunoreactive ET-1 secreted from VSMCs was mainly composed of big ET- 1, whereas approximately 90% of that from ECs was ET-1. By TGF-beta stimulation of VSMCs, the ratio of big ET-1 to ET-1 was further increased. Because big ET-1 is converted into ET-1 only on the surface of the ECs in the culture system, big ET-1 secreted from the VSMCs may function as a mediator transmitting a signal from VSMCs to ECs in vivo.