血浆氧化三甲胺水平与心力衰竭相关性研究进展

肠道菌群及其代谢产物参与各种心血管疾病的发生发展,其中与心力衰竭疾病进展的关系十分密切。该文主要讨论肠道菌群代谢物氧化三甲胺(TMAO)参与心力衰竭的病理过程以及TMAO在心力衰竭中的应用价值,介绍心力衰竭患者肠道菌群及其代谢产物的变化特点,阐明了TMAO通过介导炎症反应和相关信号通路加重心肌肥厚和心力衰竭的机制。高水平TMAO与心力衰竭患者不良结局相关,对心力衰竭的预后有较好的预测价值。通过饮食、益生菌和益生元、抗菌药物、粪便移植等途径来调节TMAO水平有望成为心力衰竭的潜在治疗手段。     

氧化三甲胺与动脉粥样硬化关系研究进展

最新研究表明,肠道菌群与代谢综合征关系密切,与其重要的靶器官心血管系统关系尤为显著。肠道菌群对胆固醇、胆汁酸的代谢直接影响血中胆固醇的水平,同时胆固醇的水平又是动脉粥样硬化形成的关键环节。本文主要对肠道菌群依赖性代谢产物氧化三甲胺(trimetlylamine oxide,TMAO)与心血管疾病发病的根源动脉粥样硬化的关系进行综述。     

肠道菌群作为心血管疾病治疗新靶点的研究现状

肠道是人体最大的消化器官和免疫器官,时刻影响着心血管疾病的发生发展过程。特别是肠道菌群产生的代谢衍生物三甲胺N-氧化物,可以增加动脉粥样硬化、促进慢性心力衰竭等心血管疾病的发生风险。采取不同措施干预肠道菌群的结构、组成及其代谢活动,可以改变循环中三甲胺N-氧化物的水平,从而影响疾病的发生发展。因此,肠道菌群心血管疾病治疗的新靶点。     

肠道微生物—动脉粥样硬化的新靶点

肠道作为机体最大的微生物群系统,肠道内微生物组成和丰度发生改变与机体的健康密切相关。动脉粥样硬化的危险因素(高龄、肥胖、饮食习惯等)诱导肠道生态失衡;肠道微生物代谢产物（短链脂肪酸、三甲胺-N-氧化物等）的改变,诱导动脉粥样硬化的发生和发展。本文就肠道微生物及其代谢产物在动脉粥样硬化中的作用和以肠道为靶点的治疗、干预的研究进展做一综述。     

肠道菌群及其代谢产物与心血管疾病关系的研究进展 #br#

心血管疾病作为目前致死致残率较高的疾病,时刻威胁着人类的健康。近年来,随着研究的不断进展,有 报道称肠道菌群及其代谢产物也参与到心血管疾病（包括与动脉粥样硬化、心力衰竭、高血压等）发生发展的过程 中。通过改善肠道菌群及其代谢产物的组成,可以改善心血管疾病的进程,而这种治疗方法也成为了一个治疗心血 管疾病的新方向。本文就肠道菌群的组成,肠道菌群代谢产物的作用,肠道菌群及其代谢产物与动脉粥样硬化、心 力衰竭、高血压等疾病的关系,通过改善肠道菌群进行疾病治疗等的研究现状进行综述。     

三甲胺N-氧化物：骨质疏松治疗的潜在靶点

三甲胺N-氧化物（trimethylamine N-oxide,TMAO）是一种在肝脏中由肝酶氧化三甲胺（trimethylamine,TMA）生成的肠道菌群代谢物。近年来，研究发现血浆TMAO水平在骨质疏松的发生与发展中发挥了重要的作用。本文介绍了TMAO的生理功能和代谢过程，以及它通过氧化应激、炎症等途径对骨质疏松发生与发展所产生的影响。血浆TMAO水平受饮食以及药物等因素的影响，这为骨质疏松的治疗和预防提供了一个新的思路和靶点。     

新型生物标志物TMAO与心血管疾病关系的研究进展

肠道菌群及其代谢产物与心血管疾病的关系是心血管领域研究的热点,有关探索肠道菌群在调节心血管生理和疾病进展中作用的基础与临床研究已取得了较大进展。国内外一些研究表明肠道微生物源代谢物三甲胺-N-氧化物（TMAO）已经成为影响心血管疾病发生发展的一个关键因素。近年来TMAO与心血管疾病的发生发展及预后关系的临床研究也取得了一些成果,血浆TMAO水平未来可作为心血管疾病危险分层、诊断及预后的新型生物标志物,对心血管疾病的发生和主要心血管事件（MACE）进行预测。本文就TMAO作为心血管疾病新型生物标志物及潜在治疗靶点的研究进展进行综述。     

基于肠心轴学说探讨肠道菌群在心血管疾病中的作用

肠道内庞大的菌群之间相互依存、相互制约,协同参与机体生理代谢和营养物质的消化。肠道菌群与心血管健康相关研究已成为十分重要的研究领域,肠道菌群组成的改变、肠道菌群产生的代谢产物和毒素都能引发心血管系统的病变。心血管疾病(cardiovascular disease,CVD)因高发病率和死亡率已成为一个主要的健康问题,CVD的发生、发展中肠道特定菌群的改变已被确定为疾病发生的关键因素。然而,肠道菌群及其代谢产物如何产生及影响CVD的潜在机制仍不清楚。本文就肠道菌群通过肠心轴调节CVD的最新研究进展进行综述,重点总结肠道微生物及其代谢产物与CVD发生发展之间复杂的相互作用,以及肠道菌群失调的改变对心血管事件发生的影响,探讨肠道菌群与CVD发病机制之间的因果联系。     

基于肠道菌群发现用于治疗Treg缺失免疫缺陷病的新药

目的肠道菌群紊乱与机体多种免疫失衡疾病的发生密切相关,如自身免疫性疾病、肿瘤和代谢综合征等。正是由于肠道菌群的稳定对人体健康至关重要,因此肠道微生态药物已经成为了现在研究与发展的热门产业。本研究挖掘肠道菌群及其代谢产物,发现可用于治疗Treg缺失免疫缺陷病的益生菌和天然产物。方法利用16S r DNA测序技术对Treg缺失介导的自身免疫性疾病模型小鼠的肠道菌群进行检测;用代谢组学技术检测模型小鼠肠道菌群代谢组谱的变化;用分子生物学、基因敲除小鼠等研究益生菌和代谢物作用的分子机制。结果在Treg缺失介导的免疫缺陷病模型小鼠上,肠道菌群发生了严重的紊乱。根据肠道菌群和代谢组谱的变化,选择罗伊氏乳酸杆菌(L. reuteri)和代谢产物肌苷处理Treg缺失小鼠,L. reuteri和肌苷通过激活腺苷受体A2AR抑制了Treg缺失引起的自身免疫性疾病。结论肠道菌群含有大量的微生物以及产生的许多独特代谢产物,可以作为新型天然药物的重要源泉,用于发现治疗自身免疫性疾病、肿瘤等疾病的新型益生菌和活性天然产物。     

异去氢钩藤碱在人和大鼠肠道菌群中代谢产物的鉴定

目的研究异去氢钩藤碱在人和大鼠肠道菌群中代谢产物的异同,阐明肠道菌群对异去氢钩藤碱在体内吸收和代谢的影响。方法采用UHPLC/Q-TOF MS技术,鉴定异去氢钩藤碱在人和大鼠肠道菌群培养液中的代谢产物。采用色谱柱为HSS C18(100 mm×2.1 mm,1.8μm)柱,流动相为乙腈-体积分数0.1%甲酸水溶液梯度洗脱,流速为0.5 m L·min-1,采用ESI离子源,正离子模式检测。结果通过与标准品比对保留时间和质谱信息,鉴定了异去氢钩藤碱在人和大鼠肠道菌群培养液中9个代谢产物。其中异构化和还原为异去氢钩藤碱在肠道菌群中的主要代谢途径,水解、羟基化和氮氧化为微量代谢途径。结论建立采用UHPLC/Q-TOF MS方法鉴定异去氢钩藤碱肠道菌群代谢产物,为四环氧化吲哚类生物碱在体内吸收和代谢机制研究提供科学依据。     

Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.     

Therapeutic Effects of Angiotensin (AT1) Receptor Antagonists

Blockade of the renin-angiotensin system improves morbidity and mortality of patients with cardiovascular diseases, e.g. arterial hypertension, renal failure, following myocardial infarction and in congestive heart failure. The angiotensin II type 1 (AT(1)) receptor antagonists (angiotensin receptor blockers; ARBs), i.e. losartan, eprosartan, irbesartan and valsartan were developed by computer-based molecule design. Early observations already indicate that the ARBs elicit pleiotropic effects developing anti-aggregatory, anti-inflammatory and anti-mitogenic effects independent from their actions at the AT(1) receptor. Losartan metabolism indicates a number of known active intermediates and pointed to further interactions of these derivatives with other receptors and cellular signaling systems. Here we discuss a compilation of detailed pharmacokinetic and pharmacodynamic data of active metabolites of ARBs indicating their mode of action and suggest novel therapeutic implications. The clinical observations that ARBs elicit potencies in patients with cardiovascular diseases via the regulation of inflammatory, growth and homeostatic factors lead us to focus on specific, reactive metabolites, which hold potential for future indications and possible drug interactions in cardiovascular diseases.     

Agents targeting inflammation in heart failure

Evidence from both experimental and clinical trials indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure (HF), contributing to cardiac remodelling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as TNF-alpha, IL-1beta and -6 in HF patients in plasma, circulating leukocytes, atherosclerotic lesions, and in the failing myocardium itself. Importantly, this rise in inflammatory mediators does not seem to be accompanied by a corresponding increase in anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta; thus resulting in an inflammatory imbalance in the cytokine network. Traditional cardiovascular drugs have little influence on the cytokine network in HF patients. Results from randomised, placebo-controlled anti-TNF studies suggest lack of effect of such therapy. Although somewhat disappointing, these negative results do not necessarily argue against the 'cytokine hypothesis'; these studies just underscore the challenges in understanding the complex cytokine network in order to develop effective treatment modalities in HF patients. More general immunmodulating treatments, such as pentoxyfylline, intravenous immunoglobulin, thalidomide and statins, have shown promising results in smaller studies, which need to be confirmed in larger studies with hospitalisations and death as the end points. In addition, further research in this area will have to be more precise in identifying the most important 'actors' in the immunopathogenesis of chronic HF.     

降糖药物对糖尿病合并心衰患者的影响

糖尿病（DM）合并心力衰竭（HF）患者在临床上治疗和生存状态较差,而不同的降糖药物导致HF的风险不同。本文综述总结了目前各类降糖药物临床实验中对HF的影响：二甲双胍是一种相对安全的降糖药物;钠-葡萄糖共转运体-2（SGLT-2）抑制剂类降糖药可以降低危重心血管病和HF的风险,未来有望用于一线治疗,以改善HF患者的预后。     

Agents targeting inflammation in heart failure

Evidence from both experimental and clinical trials indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure (HF), contributing to cardiac remodelling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as TNF-α, IL-1β and -6 in HF patients in plasma, circulating leukocytes, atherosclerotic lesions, and in the failing myocardium itself. Importantly, this rise in inflammatory mediators does not seem to be accompanied by a corresponding increase in anti-inflammatory cytokines such as IL-10 and transforming growth factor-β; thus resulting in an inflammatory imbalance in the cytokine network. Traditional cardiovascular drugs have little influence on the cytokine network in HF patients. Results from randomised, placebo-controlled anti-TNF studies suggest lack of effect of such therapy. Although somewhat disappointing, these negative results do not necessarily argue against the ‘cytokine hypothesis’; these studies just underscore the challenges in understanding the complex cytokine network in order to develop effective treatment modalities in HF patients. More general immunmodulating treatments, such as pentoxyfylline, intravenous immunoglobulin, thalidomide and statins, have shown promising results in smaller studies, which need to be confirmed in larger studies with hospitalisations and death as the end points. In addition, further research in this area will have to be more precise in identifying the most important ‘actors’ in the immunopathogenesis of chronic HF.     

Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics

Translocation of microbiome-derived lipopolysaccharide (LPS) to the bloodstream (metabolic endotoxaemia) is associated with a significantly increased risk of cardiovascular diseases (CVD); however, the direction of this association is not fully understood. It has been revealed by some studies that alterations in the intestinal microbiota (dysbiosis) lead to increased intestinal permeability and translocation of LPS to the blood circulation. LPS may trigger toll-like receptor 4- (TLR-4) mediated inflammatory responses; this could lead to a chronic low-grade pro-inflammatory condition named metabolic endotoxaemia (ME), which is typically observed in CVD patients. ME is promoted by increased intestinal permeability. Moreover, dysbiosis leads to production of trimethylamine-N-oxide (TMAO), a gut bacterial metabolite suggested as a new risk factor in CVD development. Probiotics, extensively reviewed for decades, are live microorganisms which, when taken in adequate amounts, have beneficial effects on the host metabolism. Prebiotics are a type of dietary fibre that act as nourishment for the good bacteria in the gut and decrease the population of pathogen bacteria that produce greater amounts of endotoxins. Although an association has been postulated between ME and CVD, the results of studies investigating the role of antibiotic therapy in preventing the disease have been inconsistent. In this review, we discuss how prebiotics and probiotics modulate gut microbiota and consequently might help with prevention and/or treatment of CVD associated with ME.     

COVID-19相关性心血管疾病的研究进展

新型冠状病毒肺炎（COVID-19）已迅速发展成全球卫生紧急事件。新型冠状病毒,即SARS-CoV-2,可影响多个器官,特别是肺脏和心脏。研究发现心脏生物标志物特别是超敏肌钙蛋白（hs-cTnI）和肌酸激酶（CK）的升高,在新型冠状病毒肺炎患者中很常见,有助于疾病诊断和危险分层。同时发现既往有心血管疾病的患者更易感染新型冠状病毒,其中高血压、心律失常、心肌病和冠心病是新型冠状病毒肺炎严重病例中常见的心血管疾病。如今越来越多的文献探讨了新型冠状病毒对心脏的影响,其中心肌损伤是新型冠状病毒肺炎的重要特征之一。但新型冠状病毒导致心肌损伤的确切机制尚不清楚。目前认为心肌损伤的机制包括病毒对心肌细胞的直接损伤、全身炎症反应、心肌纤维化、干扰素介导的免疫反应、1型和2型辅助性T细胞夸大的细胞因子反应、冠状动脉斑块失稳以及缺氧等。考虑到新型冠状病毒对心血管系统的复杂影响,我们需要进一步明确发病机制,以找到降低新型冠状病毒肺炎相关性急性心肌损伤发生率和死亡率的治疗方法。