3,4,5,6-四羟基(口山)酮对高糖所致血管内皮依赖性舒张功能减退的保护作用

目的:观察3,4 ,5 ,6 - 四羟基口山酮对高糖所致血管内皮依赖性舒张功能减退的保护作用。方法:在大鼠离体胸主动脉环,用高浓度葡萄糖(2 5mmol·L-1)孵育2 4h ,检测乙酰胆碱诱导的血管内皮依赖性舒张反应;人脐静脉内皮细胞株(ECV30 4 )用高浓度葡萄糖(30mmol·L-1)培养4 8h ,测定培养液中乳酸脱氢酶(LDH)活性、一氧化氮(NO)及细胞脂质过氧化物丙二醛(MDA)含量。结果:3,4 ,5 ,6 - 四羟基口山酮(1、3和10 μmol·L-1)能显著抑制高糖所致的舒血管效应减退,并且呈剂量依赖性。3,4 ,5 ,6 - 四羟基口山酮(1、3和10 μmol·L-1)能显著抑制高糖所致的内皮细胞LDH泄漏、NO释放和MDA生成的增加。结论:3,4 ,5 ,6 - 四羟基口山酮对高糖所致的血管内皮依赖性舒张功能减退有保护作用,其保护作用与抑制脂质过氧化减少血管内皮细胞损伤有关。     

糖尿病肾病药物治疗的研究

糖尿病肾病是糖尿病重要的慢性微血管并发症,长期理想控制血糖、血压和血脂等是其基本的防治措施,但近来一些有关糖尿病肾病防治的基础和临床研究表明不少药物如噻唑烷二酮类药物、血管紧张素转换酶抑制药、血管紧张素Ⅱ受体拮抗药、醛固酮受体拮抗药和他汀类药物等存在上述作用之外的肾脏保护作用,受到大家关注。     

甘糖酯抗内皮细胞损伤的研究

研究甘糖酯对Ｅｃｏｌｉ内毒素和同型半胱氨酸所致鹌鹑血管内皮损伤的保护作用。结果表明：甘糖酯能显著降低血管内皮通透性，升高血浆６－酮－ＰＧＦ１ａ含量，降低管壁脂质过氧化物代谢产物ＭＤＡ含量，且药效同给药剂量成正相关，说明甘糖酯有抗内皮损伤作用。     

罗格列酮对自发性2型糖尿病大鼠主动脉内皮细胞保护作用的实验研究

目的研究罗格列酮(胰岛素增敏剂)对自发性2型糖尿病(OLETF)大鼠血管内皮细胞的保护作用及其作用机制。方法将OLETF大鼠随机分为2组:治疗组与未治组,LETO选同种系同周龄LETO大鼠作为对照组。治疗组每日给予罗格列酮2mg·kg-1灌胃。分别于16、24周龄,观察主动脉组织形态学改变;测定主动脉胰岛素受体底物1(IRS-1)、磷脂酰肌醇3激酶(PI-3K)中p85α亚单位和内皮型一氧化氮合酶(eNOS)的蛋白表达。结果治疗组主动脉内皮细胞及血管壁病变明显减轻,主动脉IRS-1和eNOS的蛋白表达均显著高于同期未治组。结论罗格列酮可能通过干预胰岛素受体后信号传导途径,而具有直接的血管保护效应。     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

广藿香酮的药理作用研究进展

广藿香酮是从广藿香挥发油中提取的活性成分,具有广泛的药理作用。广藿香酮的药理活性及其作用机制得到了明确,包括抗炎、抗肿瘤、抗菌和抗病毒、抗氧化、胃保护、脑保护、免疫调节、杀虫。归纳总结了广藿香酮的药理活性及其作用机制,以期为广藿香酮的临床应用提供依据。     

蕲蛇酶对大鼠脑缺血再灌注损伤的保护作用

目的进一步探讨蕲蛇酶对大鼠脑缺血再灌注损伤的保护作用及其机制。方法采用线栓法制备大鼠大脑中动脉闭塞后再灌注(MCAOR)模型,观察大鼠MCAOR时神经功能状态,同时,TTC染色测脑梗死面积,电镜观察脑血管超微结构,放免法测定血浆血栓素B2及6-酮前列腺素F1α含量。用药组分别在缺血即刻或再灌注即刻静脉给药,观察比较模型组和蕲蛇酶所有给药组之间上述指标的变化。结果蕲蛇酶所有给药组都能有效改善MCAOR大鼠神经功能缺失症状,明显减小梗死灶,调节血栓素B2/6-酮前列腺素F1α,保护血管内皮细胞,维持微血管正常结构。结论蕲蛇酶对脑缺血再灌注损伤保护作用可能与维持血栓素B2/6-酮前列腺素F1α平衡、改善脑微循环有关。     

醛固酮阻断剂依普利酮在心血管疾病中的作用

肾素-血管紧张素-醛固酮系统过度激活及高醛固酮血症对心血管系统均有损伤作用。血管紧张素转化酶(ACE)抑制剂和血管紧张素受体阻断剂(ARB)已被证实可有效降低血压和保护靶器官，减少心力衰竭的发病率和死亡率；但长期使用ACE抑制剂或ARB治疗后，血醛固酮浓度又会回到基线水平，即所谓“醛固酮逃逸”，因此降低了这些药物进一步的疗效。醛固酮受体拮抗剂螺内酯对心血管系统有显著的保护作用，但它的性激素相关副作用限制了其应用。新一代选择性醛固酮受体拮抗剂依普利酮为心血管疾病的治疗开辟了新的道路。     

甘糖酯类似物MS872保护内皮细胞作用及其机制的探讨

研究了甘糖酯类似物ＭＳ８７２对同型半胱氨酸、Ｅｓｃｈｅｒｉｃｈｉａ ｃｏｌｉ内毒素和去甲肾上腺素损伤内此细胞的保护作用。结果表明，ＭＳ８７２能显著降低血管内皮细胞通透性，升高血浆６－酮－ＰＧＦ１α水平，显著降低去甲肾上腺素升高麻醉大鼠血压的作用。     

胺碘酮注射液外渗所致组织损伤和静脉炎的护理策略

目的针对胺碘酮注射液对组织和血管的影响,改变传统的静脉输液方式为专业化血管评估的程序化输液,更有效地保护患者的血管。方法对42例患者分别给于程序化的血管管理和处理。结果 42例患者中,30例出现不同程度的组织损伤和静脉炎,1例局部组织坏死经切开引流而治愈;其余29例均应用硫酸镁和(或)土豆片局部治疗痊愈。结论组织损伤和静脉炎是胺碘酮注射液的常见并发症。提高护理人员的专业技术水平,加强责任心,正确评估穿刺血管,熟练掌握该药的特点,将有效减少患者组织损伤和静脉炎的发生。     

Pharmacological effects of xanthones as cardiovascular protective agents

Many epidemiological studies indicate that consumption of dietary polyphenolic compounds is beneficial in the prevention of cardiovascular diseases. Xanthones are a class of polyphenolic compounds that commonly occur in plants and have been shown to have extensive biological and pharmacological activities. Recently, the pharmacological properties of xanthones in the cardiovascular system have attracted great interest. Xanthones and xanthone derivatives have been shown to have beneficial effects on some cardiovascular diseases, including ischemic heart disease, atherosclerosis, hypertension and thrombosis. The protective effects of xanthones in the cardiovascular system may be due to their antioxidant, antiinflammatory, platelet aggregation inhibitory, antithrombotic and/or vasorelaxant activities. In particular, the antagonism of endogenous nitric oxide synthase inhibitors by xanthones may represent the basis for improved endothelial function and for reduction of events associated with atherosclerosis.     

葡萄籽提取物化学成分及药理活性的研究进展

目的综述葡萄籽提取物的主要化学成分及药理活性的最新研究进展。方法查阅近年来的国内外相关文献,并进行归纳总结。结果发现葡萄籽提取物包括多酚类、脂质类及其他化学成分,具有抗氧化作用、心血管保护作用、抗肿瘤作用、抗辐射作用及其他药理学活性。结论葡萄籽提取物是一种很有开发价值的天然植物药。     

黄酮类化合物抗心脑血管缺血性疾病作用的研究进展

黄酮类化合物是一种广泛存在于传统中药中的次生代谢产物,拥有许多生物活性和药理作用。近年来,研究发现黄酮类化合物可以通过多种途径在缺血性脑卒中和缺血性心脏病的治疗中发挥有效的保护作用,同时对于其保护作用的机制也有了较为详细系统的阐释。比如黄酮类化合物可以在抗氧化、抑制炎症反应、细胞凋亡和自噬等病理生理机制中发挥有效作用。本文通过查阅国内外的相关文献,对黄酮类化合物抗心脑血管缺血性疾病的保护作用及其机制进行综述。旨在为抗心脑血管疾病药物的研究开发提供参考。     

钩藤生物碱对中枢神经系统的药理作用研究进展

钩藤是我国一种常用药材,对心血管系统、中枢神经系统和血液系统等均具有比较广泛的药理活性,临床上主要用于治疗高血压、焦虑等疾病。现代中药药理研究表明,钩藤对中枢神经系统的药理作用主要表现为镇静、抗癫痫、抗惊厥和对神经元的保护等,其中对神经元的保护作用与多种神经递质相关,具有多种作用机制,已被国内外越来越多的医药工作者所重视,综述钩藤生物碱对中枢神经系统的药理作用研究进展。     

丹参素衍生物的研究进展

丹参素是从中草药丹参中提取分离得到的一类酚酸件化合物。具有多种药理活性,对心血管系统具有明显的保护作用。有关丹参素衍生物的研究一直为科研人员所关注,本文对这些文献进行了系统地分析整理,旨在为进一步深入开展丹参素的结构改造和药物创新研究提供依据。     

Adiponectin circulating levels: A new emerging biomarker of cardiovascular risk

Fat is now considered as an endocrine organ that produces a lot of molecules having biological activity, called adipocytokines. Among these, adiponectin, a 247 amino acid protein produced abundantly and specifically by adipose tissue, besides its effects on glucose metabolism, plays important protective function against cardiovascular diseases. Circulating levels lower than those of healthy control subjects have found to be associated to conditions such as obesity, diabetes and cardiovascular diseases. In animal experimental models, administration of adiponectin has been shown to have beneficial effects against the development of obesity-related vascular diseases, including atherosclerosis. In humans, circulating levels can be raised by life style modification (weight loss or exercise training) or pharmacological treatments. Adiponectin is present in the human plasma in different isoforms: a large multimeric structure of high molecular weight and in a trimer and examer form, whereas the monomeric form is found only in the adipose tissue. The biological activities of the different multimers are not yet fully known, although the different isoforms appear to have different functional importance following the different diseases. This paper reports the main biological features of adiponectin in order to highlight its possible role as diagnostic/prognostic marker in cardiovascular diseases. Particular attention is paid to practical considerations relative to the analytical determination of this protein in humans.     

迷迭香酸的药理学研究进展

迷迭香酸是一种在自然界广泛分布的多酚羟基化合物,是紫苏、丹参等中草药的有效活性成分。体内、体外研究表明,迷迭香酸具有抗氧化、抗菌、抗病毒、免疫调节等药理作用,对肿瘤、器官移植排斥反应等疾病具有治疗或增效作用,对心血管系统和神经系统具有保护作用。药动学研究表明,迷迭香酸在体内可被代谢为结合态和/或甲基化的形式,主要经尿液排出体外。文中通过对近年来国内外文献的调研,从药理作用和药动学特性两方面综述了迷迭香酸的药理学研究进展。     

Cytoprotection by natural and synthetic polyphenols in the heart: novel mechanisms and perspectives

While many naturally occurring polyphenols have been shown to have therapeutic benefits against myocardial injury following ischemia-reperfusion in various experimental models, our studies have demonstrated that synthetic flavonoids may also have potent cardiac cytoprotective actions. Together with the results reported in the literature, we suggest that synthetic polyphenols may be an ideal replacement for natural compounds in the development of myocardial protective drugs. Polyphenols exert myocardial protective effects via antioxidant activities, preservation of nitric oxide, antiinflammatory activities and modulation of matrix metalloproteinases. Recent studies have identified some novel mechanisms that may also contribute to polyphenol-induced myocardial protection, including prevention of mitochondrial dysfunction, pharmacological preconditioning, and modulation of the function of enzymes involved in epigenetic modifications such as histone acetyltransferases. In addition to the protective effects against acute myocardial injury, there has been experimental evidence showing that polyphenols may also modulate the development of cardiac hypertrophy, ventricular remodeling and fibrosis after myocardial infarction.     

On- and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors

Lowering of serum low-density lipoprotein cholesterol (LDL-C) levels remains the primary aim of lipid management. Much progress has been made in reducing rates of cardiovascular disease morbidity and mortality, largely through increased awareness of lipid-lowering therapies and particularly through the use of high-efficacy LDL-C-lowering HMG-CoA reductase inhibitors (statins). While statins have been effective in reducing cardiovascular disease risk, many patients do not adequately achieve guideline-recommended LDL-C goals and may benefit from additional cholesterol management therapies. Low serum levels of high-density lipoprotein cholesterol (HDL-C) are considered another important determinant of cardiovascular disease risk, and increased serum HDL-C levels have been shown to be associated with reductions in the incidence of cardiovascular disease. One approach toward raising serum HDL-C levels is the inhibition of cholesteryl ester-transfer protein (CETP), a plasma protein that promotes the transfer of cholesteryl ester from HDL particles and other lipoprotein fractions to pro-atherogenic apolipoprotein B-containing lipoproteins. The inhibition of this protein raises HDL-C levels and also reduces LDL-C levels. The concept of raising HDL-C levels through pharmacological intervention of this target was validated in preclinical and clinical studies with torcetrapib, the first CETP inhibitor to be assessed in late-stage clinical trials. The large clinical outcomes trial, ILLUMINATE, was prematurely terminated due to other unexpected pharmacological effects of torcetrapib that led to an increased risk of cardiovascular events and deaths. Thus, the ultimate effect of CETP inhibition on cardiovascular disease outcomes remains to be determined. Other CETP inhibitors currently in development do not have the adverse effects of increased blood pressure and circulating levels of aldosterone shown to be structurally related to torcetrapib. Preclinical and pharmacology studies have shown that these CETP inhibitors are distinct compared with torcetrapib and lack the features related to its off-target pharmacology. These findings indicate that the off-target activities of torcetrapib are not necessarily class effects of CETP inhibitors. Recent clinical trials have shown that dalcetrapib, anacetrapib and evacetrapib, the most advanced of these compounds in development, effectively raise HDL-C levels and lower LDL-C in the absence of off-target activities. The results of these trials are encouraging within the limits of study size and duration and provide a rationale for conducting further studies, including large clinical outcomes trials to assess whether CETP inhibition can lead to cardioprotective effects. This review summarizes the data supporting the development of CETP inhibitors as HDL-C-raising therapy, including structure-activity relationships and preclinical and clinical pharmacology studies of known CETP inhibitors.     

General pharmacology of cicletanine

Cicletanine is a new antihypertensive molecule which acts directly on vascular smooth muscle by increasing prostacyclin synthesis and interacting with various agents which mobilize intracellular Ca2+ ions. General pharmacological studies have shown that in the anaesthetized normotensive dog, cicletanine does not induce tachycardia (even at high doses) and does not modify aortic, femoral or coronary blood flow. Moreover, cicletanine shows a protective effect on vascular permeability and capillary hyperpermeability. This protective action on the vascular wall is of importance, since one of the direct vascular consequences of arterial hypertension is a fragilisation of vessel walls, tissue oedema and even vascular rupture. Cicletanine slows down the thrombogenic process initiated by electric arterial stimulation. Retardation of the thrombogenic process by the drug may be explained by the stimulation that cicletanine exerts on the synthesis and production of prostacyclin. Behavioural studies in mice, rats and primates have shown that cicletanine has no sedative effects, even at very high doses. General pharmacological studies have demonstrated that both cardiovascular function and the central nervous system are equally tolerant to cicletanine. Cicletanine is an antihypertensive agent which has no effect on cardiovascular haemodynamics and is able to prevent some rheological and vascular-linked cardiac risks of hypertension.