厚朴酚与和厚朴酚对脑损伤的保护作用及其机制的研究进展

整体实验结果显示,厚朴酚与和厚朴酚对缺氧、缺血、缺血再灌注、出血、高热中暑和脓毒症引起的脑损伤有保护作用。离体实验也证实,厚朴酚与和厚朴酚能对抗化学性缺氧、葡萄糖缺乏、缺血再灌注、高热,以及过氧化氢(H₂O₂)、兴奋性神经递质 N-甲基-D-门冬氨酸(NMDA)和谷氨酸、三甲基锡引起的神经细胞损伤。这都提示,厚朴酚与和厚朴酚可能是通过直接清除氧自由基和提高机体的抗氧化酶活性而间接清除氧自由基,以及阻滞磷脂酰肌醇 3-激酶(PI3K)-蛋白激酶 B(Akt)、胞外信号调节激酶(ERK)-促分裂素原活化蛋白激酶(MAPK)和 Toll 样受体(TLR)/MAPK/核因子 κB(NF-κB)等信号通路而抑制炎性细胞因子表达,从而产生抗氧化和抗炎作用,进而发挥脑保护作用。此外,厚朴酚与和厚朴酚还可通过促进抑制性神经递质 γ-氨基丁酸的生物合成和增强 γ-氨基丁酸的受体结合能力,从而对抗兴奋性神经递质对神经细胞的伤害。该文综述了厚朴酚与和厚朴酚对脑损伤的保护作用及其机制,并对其研究进展做了分析。     

红景天苷及其苷元酪醇的心血管保护作用

本文综述了红景天苷及其苷元酪醇对心血管的主要保护作用:①抗氧化作用,促进一氧化氮合成和抑制炎症介质前列腺素合成。②激活PI3K/Akt信号转导通路,上调缺氧诱导因子-1和血管内皮生长因子表达及Bcl-2/Bax比值。③抑制线粒体通透性转换孔开放,维护线粒体跨膜电位,阻滞半胱天冬酶-3激活,保护心肌细胞和血管内皮细胞。红景天苷和酪醇对抗缺血、缺氧、缺血再灌注或氧化应激引起的心血管细胞损伤,抑制氧化修饰的低密度脂蛋白形成、血管平滑肌细胞增殖和血小板聚集,降低血液粘度等,阻碍动脉粥样硬化发生和发展,产生心血管保护作用。     

中药厚朴及其成分厚朴酚与和厚朴酚体外抗各种球菌的药理作用研究进展

中药厚朴不同溶剂的粗提取物具有体外抗各种球菌的药理作用,其中厚朴石油醚和乙醇提取物的抗球菌作用最强.厚朴酚(magnolol)及和厚朴酚(honokiol)是中药厚朴抗球菌的主要活性成分,其中厚朴酚抗球菌作用稍强于和厚朴酚.厚朴酚及和厚朴酚均能抑制金黄色葡萄球菌(以下简称"金葡菌")的自溶酶和α-溶血素、肠毒素-A、肠毒素-B的表达,阻断金葡菌的自溶和抑制其黏附功能及毒力,阻滞球菌诱导宿主细胞的炎性损伤反应.厚朴酚及和厚朴酚均能抑制被膜态金葡菌合成和释放eDNA和PIA,进而抑制生物被膜的形成,降低球菌的自我保护能力,产生抗球菌作用.本文中综述了中药厚朴及其成分厚朴酚及和厚朴酚体外抗各种球菌的药理作用,并对其研究进展做了分析.     

氧化苦参碱心脏保护作用的研究进展

氧化苦参碱对心脏具有正性肌力、负性频率和负性自律性的作用,因此具有广谱抗心律失常作用。氧化苦参碱对冠脉狭窄缺血、缺血再灌注以及异丙肾上腺素、阿霉素、感染和免疫引起的心肌损伤都有保护作用,并能阻滞心肌肥大和纤维化发生发展。氧化苦参碱心脏保护作用的基本机制是其抗氧化、抗炎和免疫抑制以及抑制盐皮质激素（醛固酮）受体的表达,产生心肌保护作用。即通过激活Nrf2/HO-1信号通路和抑制转化生长因子（TGF）-β1及I型TGF-β1受体的表达,从而抑制下游的JAK/STAT、MAPK/Smad2/3和Notch的信号通路的机制,减少心肌细胞凋亡,减轻心肌损伤和抑制胶原合成,产生抑制心肌肥大和纤维化的作用。     

红景天苷心脏保护药理作用的研究进展

红景天苷通过促进心肌细胞肌浆网释放Ca²⁺,增强心肌收缩力,又可上调肌浆网钙泵的表达和下调钙调神经磷酸酶的表达,促进Ca²⁺返回肌浆网,阻滞钙超载引起的心肌损伤,有利于改善心功能。红景天苷通过抗氧化和抗炎作用,抑制心脏脂质过氧化反应,提高心脏组织的抗氧化酶活性,抑制炎性细胞因子表达和线粒体通透性转换孔开放,阻滞心肌细胞凋亡;也可通过上调缺氧诱导因子和血管内皮生长因子表达,促进缺血心肌血管形成,改善心肌缺血;还通过上调PGC-1α-NRF-1/NRF-2表达的通路,改善心肌线粒体呼吸功能,最终产生心脏保护作用。基于上述作用机制,红景天苷可对抗缺氧、缺血、缺血再灌注、力竭运动、化学品、生物毒素等引起的心脏损伤。     

熊果酸和齐墩果酸对心脏保护作用的研究进展

熊果酸和齐墩果酸通过抗氧化作用,抑制心脏脂质过氧化反应,提高心脏组织的抗氧化酶活性和非酶抗氧化物质水平,阻滞心肌细胞凋亡,产生心脏保护作用。熊果酸和齐墩果酸还可通过激活ATP敏感性钾通道并促进心房利钠肽合成和分泌,产生心脏保护作用。熊果酸和齐墩果酸也可通过抑制血管紧张素Ⅱ诱导心肌成纤维细胞增殖、转化生长因子-β_1表达、胶原合成和分泌,阻滞心肌纤维化形成。熊果酸和齐墩果酸的以上作用被认为是它们对抗异丙肾上腺素、乙醇、高血糖、高血压缺血、缺血再灌注引起心脏损伤的主要机制。熊果酸和齐墩果酸还具有免疫调节作用,能抑制T细胞核因子-κB核易位和T细胞活化,因此能防治实验性自身免疫性心肌炎和抑制机体对心脏移植物的排异反应。综述熊果酸和齐墩果酸对心脏保护作用的文献,并对其研究进展作了分析。     

苦参碱的心脏保护作用及其机制的研究进展

苦参碱对心脏具有正性肌力、负性频率和负性自律性的作用,因此具有广谱的抗心律失常作用。苦参碱对冠脉结扎缺血、缺血再灌注、异丙肾上腺素、高血脂、糖尿病和阿霉素引起的心肌损伤都有保护作用。苦参碱还能阻滞心肌肥大和纤维化的发生、发展。苦参碱保护心脏作用的基本机制是抗氧化、抗炎、降血糖、调血脂作用,由此抑制ROS/TLR4信号通路、PI3K/Akt信号通路和TGF-β诱导的PERK信号通路,激活Akt和STAT3信号通路和AMPKα/UCP2信号通路,上调JAK2/STAT3通路上的HSP70以及JNK、ASK1、e NOS和一氧化氮的表达,提高线粒体ATP酶活性,保护线粒体而减少心肌细胞凋亡、减轻心肌损伤和抑制胶原合成,从而抑制心肌肥大和纤维化。从抗各种心肌缺血性损伤、抗阿霉素诱导的心肌损伤、抗高糖性心肌损伤、抗心肌肥大和纤维化4个方面综述苦参碱的心脏保护作用及其机制。     

和厚朴酚及厚朴酚抗结直肠癌和胃癌药理作用及其机制的研究进展

和厚朴酚及厚朴酚是疏水性联苯酚类结构的同分异构体。和厚朴酚能防治结直肠癌CT26细胞或RKO细胞移植瘤在小鼠体内生长,并延长荷瘤小鼠的生存时间。体外实验发现和厚朴酚及厚朴酚能浓度相关地抑制结直肠癌SW480细胞、SW620细胞、LoVo细胞、LS180细胞、CT26细胞、RKO细胞、Caco-2细胞、COLO-205细胞、HCT-8细胞、HCT15细胞、HCT116细胞增殖,并诱导细胞凋亡。在HCT116细胞中,hMLH1错配修复缺失型细胞对和厚朴酚的敏感性高于完整型细胞。和厚朴酚是通过调控JNK/Nur77/AMPK、TGF-β1/p38MAPK/Hippo、BMP7/TGF-β1/p53和BMP7/PTEN/AKT 4条信号转导通路诱导结直肠癌细胞凋亡,还通过抑制血管内皮生长因子的表达,阻滞肿瘤内新生血管形成,抑制结直肠癌生长。和厚朴酚及厚朴酚还能抑制胃癌MGC-803细胞和SGC-7901细胞的增殖。     

厚朴酚及和厚朴酚防治高血糖、高脂血症及其并发症的药理机制研究进展

厚朴酚及和厚朴酚是来自于中药厚朴的同分异构体,具有相同的药理活性。它们都可通过保护胰腺β-细胞,促进胰岛素分泌,提高血中胰岛素水平及细胞对葡萄糖的摄取和利用,从而降低胰岛素抵抗和血糖水平;还能通过抑制脂质合成和促进脂质分解,产生调血脂作用。厚朴酚及和厚朴酚可通过降血糖、调血脂及抗氧化作用,从源头上减少氧化低密度脂蛋白（ox-LDL）和晚期糖基化终末产物（AGEs）的生成,还可通过抗氧化、抗炎及细胞保护作用,保护心血管系统、肾脏、肝脏、胰腺等组织器官对抗高血糖、高脂血症诱导并发症的发生和发展。因此厚朴酚及和厚朴酚有开发成为治疗代谢综合征新药的潜力。     

胰高血糖素样肽-1的心血管益处及机制

心血管疾病是2型糖尿病患者的主要死亡原因之一。新近研究发现胰高血糖素样肽-1(GLP-1)不仅通过葡萄糖依赖的方式刺激胰岛素分泌和抑制糖原的不适当分泌,延缓胃排空,增加饱食感等方式调节血糖;还能通过GLP-1R和受体以外的方式发挥心血管保护作用,包括心肌、内皮细胞和血管等。越来越多的动物和临床研究显示,GLP-1和GLP-1R激动剂都能改善内皮细胞功能、促进钠的排泄、改善缺血损伤的心肌和心功能的恢复,减少心血管风险的危险因素和标志物。文中综述有关动物和人类研究中GLP-1对心血管系统的作用以及可能机制。     

Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors

Accumulating evidence suggests that the reactive oxygen and nitrogen species are generated in cardiomyocytes and endothelial cells during myocardial ischemia/reperfusion injury, various forms of heart failure or cardiomyopathies, circulatory shock, cardiovascular aging, diabetic complications, myocardial hypertrophy, atherosclerosis, and vascular remodeling following injury. These reactive species induce oxidative DNA damage and consequent activation of the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), the most abundant isoform of the PARP enzyme family. PARP overactivation, on the one hand, depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to the functional impairment or death of the endothelial cells and cardiomyocytes. On the other hand, PARP activation modulates important inflammatory pathways, and PARP-1 activity can also be modulated by several endogenous factors such as various kinases, purines, vitamin D, thyroid hormones, polyamines, and estrogens, just to mention a few. Recent studies have demonstrated that pharmacological inhibition of PARP provides significant benefits in animal models of cardiovascular disorders, and novel PARP inhibitors have entered clinical development for various cardiovascular indications. Because PARP inhibitors can enhance the effect of anticancer drugs and decrease angiogenesis, their therapeutic potential is also being explored for cancer treatment. This review discusses the therapeutic effects of PARP inhibitors in myocardial ischemia/reperfusion injury, various forms of heart failure, cardiomyopathies, circulatory shock, cardiovascular aging, diabetic cardiovascular complications, myocardial hypertrophy, atherosclerosis, vascular remodeling following injury, angiogenesis, and also summarizes our knowledge obtained from the use of PARP-1 knockout mice in the various preclinical models of cardiovascular diseases.     

铁屎米酮对大鼠心肌缺血再灌注损伤的保护作用

目的：研究铁屎米酮对心肌缺血再灌注损伤的保护作用。方法：大鼠左冠脉前降支结扎造成心肌缺血再灌注损伤。结果：铁屎米酮(5,10及20 mg.kg^-1,ig)可显著降低缺血再灌性心律失常发生率,缩短心律失常持续时间,防止室颤的发生;减少心肌丙二醛含量,提高心肌超氧物歧化酶活性;减轻心肌细胞超微结构损伤。结论：铁屎米酮对心肌缺血再灌注损伤有保护作用。     

白芍总苷的心血管保护效应及其作用机制的研究进展

白芍总苷可以改善动脉粥样硬化程度和心肌重构、减轻心肌缺血、缩小心肌梗死面积、减轻心肌缺血再灌注损伤,具有心肌和血管保护作用,其机制与调节血脂、抗血小板聚集、抑制氧化应激、减轻炎症损伤、抑制细胞凋亡/焦亡相关.通过系统梳理文献,深入探讨白芍总苷的心血管保护效应及其作用机制,为白芍总苷防治心血管疾病提供新策略.     

Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation

Abstract

Cerium oxide (CeO₂) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO₂ exposure may influence pulmonary or systemic inflammation. Furthermore, how mast cells would influence inflammatory responses to a nanoparticle exposure is unknown. We thus compared pulmonary and cardiovascular responses between C57BL/6 and B6.Cg-Kit^W-sh mast cell deficient mice following CeO₂ nanoparticle instillation. C57BL/6 mice instilled with CeO₂ exhibited mild pulmonary inflammation. However, B6.Cg-Kit^W-sh mice did not display a similar degree of inflammation following CeO₂ instillation. Moreover, C57BL/6 mice instilled with CeO₂ exhibited altered aortic vascular responses to adenosine and an increase in myocardial ischemia/reperfusion injury which was absent in B6.Cg-Kit^W-sh mice. In vitro CeO₂ exposure resulted in increased production of PGD₂, TNF-α, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO₂ nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury.     

Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation

Cerium oxide (CeO?) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO? exposure may influence pulmonary or systemic inflammation. Furthermore, how mast cells would influence inflammatory responses to a nanoparticle exposure is unknown. We thus compared pulmonary and cardiovascular responses between C57BL/6 and B6.Cg-Kit(W-sh) mast cell deficient mice following CeO? nanoparticle instillation. C57BL/6 mice instilled with CeO? exhibited mild pulmonary inflammation. However, B6.Cg-Kit(W-sh) mice did not display a similar degree of inflammation following CeO? instillation. Moreover, C57BL/6 mice instilled with CeO? exhibited altered aortic vascular responses to adenosine and an increase in myocardial ischemia/reperfusion injury which was absent in B6.Cg-Kit(W-sh) mice. In vitro CeO? exposure resulted in increased production of PGD?, TNF-α, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO? nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury.     

The Use of Diltiazem Hydrochloride in Cardiovascular Disorders

Diltiazem, a calcium channel blocking agent, has potent cardiovascular effects that are directly related to its influence on vascular smooth muscle, ventricular myocardium, and specialized conducting tissue. It causes coronary and peripheral vasodilation, has a negative chronotropic and dromotropic effect, and little to no negative inotropic effect in patients with normal ventricular function. Diltiazem has potential use in a wide variety of cardiovascular disorders. It has been shown extremely effective in relieving the coronary artery spasm associated with variant angina. When compared with nitrates in patients with exertional angina, diltiazem has similar efficacy. Preliminary work indicates it will have a therapeutic role in the treatment of unstable angina. Because of its ability to improve the balance between myocardial oxygen supply and demand and reduce cellular injury secondary to ischemia, it is likely that diltiazem will be of benefit in the treatment of acutely ischemic myocardium during cardiopulmonary bypass and possibly acute myocardial infarction. It has proven efficacy in treating re-entrant supraventricular tachycardia. Adverse effects are seen in less than 5% of patients, indicating that it is well tolerated.     

参芪培元口服液保护急性心肌缺血损伤的机制研究

目的:研究参芪培元口服液预处理对急性心肌缺血大鼠心血管的保护作用.方法:设假手术组、模型对照组、维拉帕米组、参芪培元口服液组,建立急性心肌缺血模型.造模后2 h时采血测血浆内皮素(ET)、降钙素基因相关肽(CGRP)、循环内皮细胞(CEC)计数,并进行心肌病理形态学观察.结果:参芪培元口服液和维拉帕米均可显著降低急性心肌缺血大鼠血浆ET和CEC水平,减轻心肌病理形态学改变.同时两组的血浆CGRP均显著低于模型对照组(P＜0.05).参芪培元口服液组和维拉帕米组间的上述3指标无显著性差异.结论:参芪培元口服液预处理可减轻心肌及血管内皮细胞损伤,调节急性心肌缺血时所发生的ET,CGRP分泌失衡.     

Alpha-lipoic acid protects against myocardial ischemia/reperfusion injury via multiple target effects

Myocardial ischemia/reperfusion (MI/R) is a major cause for the events of cardiovascular disease. Oxidative stress plays a critical role in the development of ischemia/reperfusion (IR) injury. As a potent antioxidant, alpha-lipoic acid (LA) has been shown to provide a benefit for the inhibition of IR injury and inhibit reactive oxygen species (ROS) generation during MI/R in rats. However, the mechanism on the protective effect of LA is still to be clarified. The present study was aimed to investigate the protective effect of LA against MI/R injury and its mechanisms. We found that 2 h of myocardial ischemia followed by different time periods of reperfusion resulted in significant increase of creatine kinase (CK) activity. MI/R also significantly promoted oxidative stress and decreased the activities of antioxidant enzymes. In addition, apoptosis and inflammatory response were activated and aggravated in a time-dependent manner by MI/R. All these alterations induced by MI/R were attenuated by the administration of LA 30 min before reperfusion. These results suggested that LA played a protective effect against MI/R injury via antioxidant, anti-apoptotic and anti-inflammatory effects. These findings may significantly better the understanding of the pharmacological actions of LA and advance therapeutic approaches to MI/R injury and cardiovascular diseases.     

三七总皂苷对心血管作用的药理研究新进展

本文主要综述近5年三七总皂苷（PNS）对心血管系统作用的药理研究进展。研究证明，PNS除具有降血压、扩张血管、抗心律失常等生理活性外，还具有抑制心肌缺血．再灌注损伤、钙拮抗、减轻心肌损伤、对抗心肌肥大和心室重构作用，以及抑制血管平滑肌细胞的增殖、血拴形成和动脉粥样硬化及保护血管内皮细胞等的药理作用。提出应从其对细胞膜受体、细胞核受体及离子通道的作用及整体水平、细胞水平、分子水平或基因水平的表达，揭示PNS的药理作用机制。