肝脏疾病的导向治疗

肝脏疾病的治疗效果受到很多因素的影响。其中之一就是治疗药物或治疗技术不能有效地到达肝脏部位,或者不能相对集中在肝脏。解决这类问题的办法就是探索肝脏疾病导向治疗的新方法。目前具有应用前景的研究方向,主要是根据肝脏去唾液酸糖蛋白受体（ASGR）特点设计的肝脏疾病导向治疗,以及应用病毒特异性抗体的导向治疗。一、去唾液酸糖蛋白受体导向治疗去唾液酸糖蛋白受体是肝细胞膜上特异性表达的受体类型,可以与半乳糖或半乳糖胺集团结合。因此,将肝脏疾病的治疗药物进行半乳糖化修饰,就能使其通过与ASGR之间的特异性结合,实现…     

趋化因子受体CCR7在心血管疾病中的研究进展

心血管疾病可能由免疫炎症反应引起,而趋化因子及其受体在免疫炎症反应中起着关键的作用,提示其与心血管疾病的发生、发展密切相关。本文就趋化因子受体CCR7在动脉粥样硬化、心肌病、心力衰竭以及心脏移植排斥反应等疾病的发病过程中的作用做一综述。     

DNA甲基化与心血管疾病研究进展

心血管疾病严重威胁人类健康,其发生发展是遗传因素和环境因素相互作用的复杂过程。表观遗传修饰是连接环境与遗传因素的桥梁。表观遗传包括DNA甲基化、基因组印记、染色质组蛋自修饰、RNA编辑等各种基因调控方式。近些年研究发现表观遗传在心血管疾病的发生发展中起着重要的作用。初步的研究发现动脉粥样硬化、高血压病、肥厚性心肌病和心律失常等相关候选基因表达和DNA甲基化修饰之间有一定的关联性,如雌激素受体(ER)基因甲基化异常可能参与动脉粥样硬化的发生,血管紧张素I b型受体(AT1b)编码的基因低甲基化与高血压发病可能相关,血浆血栓调节蛋白(TM)启动子区高甲基化状态可能介导冠心病的发病等。本文就近年来心血管疾病中DNA甲基化的作用的研究进展进行综述。     

肝癌细胞膜受体含pRSVB7特异性配基的构建

目的针对肝癌细胞HLA-B7基因的表达缺陷和具有细胞特异性的去唾液酸a1酸性糖蛋白受体的特点,构建了含HLA-B7基因的该特异性受体的配基,为肝癌的基因治疗准备了物质条件.方法以多聚(L)赖氨酸为联接桥,用碳二亚胺交联法合成去唾液酸α1酸性糖蛋白-多聚(L)赖氨酸-HLA-B7真核表达质粒复合物.结果经电泳鉴定,产物的分子量和电泳行为与预期的一致.结论本文所用的方法可行,能获得预期的产物.     

L—HSA—Ara—AMP识别的去唾液酸糖蛋白受体在大鼠肝细胞及HepG …

以胶体金标记抗病毒交联物Ｌ－ＨＳＡ－Ａｒａ－ＡＭＰ，做直接胶体金银染色，光镜观察该交联物识别的去唾液酸糖蛋白受体在大鼠肝细胞及ＨｅｐＧ－２细胞表面的定位，同时分别用大鼠脾组织，金标ＨＳＡ做对照。结果：去唾液酸糖蛋白受体多布在大鼠肝细胞的血窦面，侧面亦有少量分布，ＨｅｐＧ－２细胞表面受体呈阳性，而两组对照组受体标记均呈阴性。     

L－HSA－Ara－AMP识别的去唾液酸糖蛋白受体在大鼠肝细胞及HepG－2细胞表面的定位

以胶体金标记抗病毒交联物Ｌ－ＨＳＡ－Ａｒａ－ＡＭＰ，做直接胶体金银染色，光镜观察该交联物识别的去唾液酸糖蛋白受体在大鼠肝细胞及ＨｅｐＧ－２细胞表面的定位，同时分别用大鼠脾组织，金标ＨＳＡ做对照。结果：去唾液酸糖蛋白受体多分布在大鼠肝细胞的血窦面，侧面亦有少量分布。ＨｅｐＧ－２细胞表面受体呈阳性。而两组对照组受体标记均呈阴性。     

CD36抗原与动脉粥样硬化

CD36抗原是一种细胞膜糖蛋白；它既是粘附分子，又是清道夫受体，参与包括动脉粥样硬化在内的许多生理和病理过程。本文介绍CD36抗原的生物学特性及其在动脉粥样硬化发生中的作用。     

神经氨酸酶1在心血管疾病中的研究进展

神经氨酸酶(NEU)是一类分解细胞表面唾液酸的酶。在哺乳动物中,NEU分为NEU1、NEU2、NEU3和NEU4四种类型,其中NEU1作用最为广泛,现已被证明在神经系统疾病、呼吸系统疾病和癌症等疾病的发生发展中起重要作用。近年来,NEU1在心血管中的作用也逐渐得到重视,尤其是在动脉粥样硬化、缺血再灌注损伤、心力衰竭和心肌病等心血管疾病中扮演着重要角色,现对NEU1在上述心血管疾病方面的作用进行综述。     

细胞间黏附分子-1与心血管疾病关系研究进展

细胞间黏附分子-1(intercellularadhesionmolecule-1,ICAM-1)是一种相对分子质量为76×103～114×103的单链跨膜糖蛋白,属于免疫球蛋白超家族成员之一,它通过识别其受体介导细胞-细胞间的黏附,参与多种炎症反应及免疫过程。近年来其与心血管疾病越来越受到重视,本文综述近年来国内外学者对ICAM-1与心血管疾病的关系。     

蛋白磷酸化对胞核因子-kB活化的调节

ＣＤ３６抗原是一种细胞膜糖蛋白;它既是粘附分子,又是清道夫受体,参与包括动脉粥样硬化在内的许多生理和病理过程。本文介绍ＣＤ３６抗原的生物学特性及其在动脉粥样硬化发生中的作用。     

C‐C Chemokine Receptor 2 Expression by Circulating Monocytes Influences Atherosclerosis in Patients on Chronic Hemodialysis

Mortality from cardiovascular or cerebrovascular disease due to atherosclerosis is increased in patients on chronic hemodialysis. Monocyte chemoattractant protein‐1 and its receptor, C‐C chemokine receptor 2, play an important role in recruiting monocytes to atherosclerotic lesions. The relationship between atherosclerosis in hemodialysis patients and C‐C chemokine receptor 2 expression is unknown. Fifty‐six patients on chronic hemodialysis and 27 age‐ and sex‐matched controls were enrolled. Serum levels of monocyte chemoattractant protein‐1 and expression of C‐C chemokine receptor 2 by circulating monocytes were determined. Atherosclerosis was evaluated from the carotid intima‐media thickness and cardio‐ankle vascular index. Serum levels of monocyte chemoattractant protein‐1 and expression of C‐C chemokine receptor 2 by monocytes were significantly higher in the hemodialysis patients than the controls. Multiple regression analysis showed a positive correlation between receptor expression and both indexes of atherosclerosis. C‐C chemokine receptor 2 expression by circulating monocytes influences atherosclerosis in patients on chronic hemodialysis.     

Novel Immune Signals and Atherosclerosis

Atherosclerosis underlies coronary artery disease (CAD) and cerebrovascular disease, which are the most common forms of life-threatening cardiovascular disorders. To minimize the risk of atherosclerotic complications, primary and secondary prevention strategies seek to control risk factors. Reducing low-density lipoprotein (LDL) cholesterol through lipid-lowering drugs, such as statins, in particular yields a proportional decrease in cardiovascular disease risk. Atherosclerosis is considered to be a complex chronic inflammatory process triggered by cardiovascular risk factors which cause endothelial dysfunction and inflammatory cell infiltration within the artery wall. In this review, we summarize the current understanding of the underling molecular mechanisms of the immune signals in the development and progression of atherosclerosis. Among various molecular mechanisms, toll like receptors (TLRs) are potent proinflammatory cytokines that operate to induce inflammation play an important role in the pathogenesis of atherosclerosis. Moreover, we discuss current knowledge regarding monocyte/macrophage biology that contributes to the progression of atherosclerosis, including macrophage polarization and heterogeneity. Understanding the molecular mechanisms in conjunction with orchestration of monocyte/macrophage biology should provide a basis for novel treatment strategies to prevent the development and progression of atherosclerosis.     

Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis

Atherosclerosis is the primary ischaemic vascular condition underlying a majority of cardiovascular disease related deaths. Endothelin-1 is a vasoactive peptide agent upregulated in atherosclerosis and in conjunction with its G protein-coupled receptors exerts diverse actions on all cells of the vasculature in particular vascular smooth muscle cells (VSMC). The effects of endothelin-1 include cell proliferation, migration and contraction, and the induction of extracellular matrix components and growth factors. VSMC as the major component of the neointima in atherosclerotic plaques accordingly play a key role in atherogenesis. In this review we examine classic and novel signalling pathways activated by endothelin-1 in VSMC (including phospholipase C, adenylate cyclase, Rho kinase, transactivation of receptor tyrosine kinases, mitogen activated protein kinase cascades and beta-arrestin) and their likely impact on the development and progression of atherosclerosis.     

DNA甲基化与动脉粥样硬化

动脉粥样硬化是心血管疾病致残致死的主要原因,现有的一些学说还不足以解释其病理机制。DNA甲基化修饰是一种从遗传中获得的,使DNA发生甲基化修饰的表遗传调控过程。基因组DNA甲基化模式改变会直接或间接抑制基因转录,影响基因表达。现有的研究提示DNA甲基化可能参与动脉粥样硬化的发生发展,本文将重点阐述什么是DNA甲基化,DNA甲基化与动脉粥样硬化及其危险因素的研究进展。     

牙周炎促进动脉粥样硬化的机制

牙周炎作为一种常见病,被认为与许多系统性疾病密切相关,尤其是心血管疾病。动脉粥样硬化是心血管疾病发生发展的基础病变。近年来的研究表明牙周炎可促进动脉粥样硬化的发生与发展。文章回顾牙周炎在促进动脉粥样硬化方面的相关证据,重点探讨其促进动脉粥样硬化的相关机制,为临床诊治提供新思路。     

动脉粥样硬化与Salusins相关性研究进展

动脉粥样硬化是一种常见的心血管疾病,为心脑血管疾病的最主要病理基础,近年来其发病率和死亡率显著上升,成为迫切要解决的关键问题。Salusins是一种新的血管活性肽,大量研究表明在动脉粥样硬化斑块中Salusins高表达,在动脉粥样硬化发生和进展中发挥重要作用,成为一个新的治疗靶点。文章对该领域的最新研究进展做一综述,探讨国内外有关动脉粥样硬化与Salusins的研究现状,并提出未来在该领域中的展望。     

What effects might anti-TNFalpha treatment be expected to have on cardiovascular morbidity and mortality in rheumatoid arthritis? A review of the role of TNFalpha in cardiovascular pathophysiology

Patients with rheumatoid arthritis (RA) have an increased burden of atherosclerotic cardiovascular disease which cannot be explained by an increased prevalence of traditional cardiovascular risk factors alone. Atherosclerosis is now being viewed as an inflammatory condition and the cumulative inflammation experienced in RA may contribute to accelerated atherosclerosis. It has been hypothesised that treatment with anti-tumour necrosis factor (TNF) alpha in RA may reduce both intra-articular inflammation and the inflammation associated with atherosclerosis. Thus, TNFalpha blockade may reduce the cardiovascular morbidity and mortality associated with RA. This review examines the pathophysiological role of TNFalpha in atherosclerosis and the evidence to date that anti-TNFalpha treatment modifies this process in RA.     

Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists in Atherosclerosis Prevention

Atherosclerosis is a highly complex biological process that has become the scourge of modern civilization. Endothelial dysfunction is the first step in the development of atherosclerosis. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development of endothelial dysfunction and atherosclerosis. Several studies have shown that in vitro blockade of the RAAS is associated with improvement in markers of endothelial dysfunction and inflammation. Many clinical trials have demonstrated a clear benefit of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) manifested by a reduction of cardiovascular events. These findings suggest that ACEIs and ARBs can play an important role in prevention of atherosclerosis and in the delay of its progression. In this review we focus on the importance of RAAS blockade to prevent or delay progression of atherosclerosis and its impact on reduction of cardiovascular events.     

抗动脉粥样硬化疫苗研究进展

动脉粥样硬化是引起心脑血管疾病的主要原因.研究证实,在动脉粥样硬化发生和发展的整个进程中都有免疫反应的参与.通过接种疫苗治疗动脉粥样硬化正在成为人们关注的热点.现就近年来接种疫苗治疗动脉粥样硬化这方面的研究报道进行综述,介绍此方面的最新进展.     

乙酰肝素酶与动脉粥样硬化

动脉粥样硬化是致死率较高的常见心血管疾病,乙酰肝素酶是能够裂解细胞外膜中硫酸乙酰蛋白多糖上侧链乙酰肝素的一种内切性β-D-葡萄糖醛酸糖苷酶,且其非酶活性也在许多正常生理活动或病理疾病中发挥作用.研究表明乙酰肝素酶与动脉粥样硬化的形成和进展有着紧密的联系.本文综述了乙酰肝素酶损伤内皮、促凝、诱导炎症因子及脂质聚集等作用,...