脂质组学在疾病生物标记物研究应用现状

脂质组学通过研究脂质的结构和功能及其在体内的代谢变化,明确其对疾病诊断和治疗的作用,以期提高疾病风险预测的能力。常用脂质组学分析方法包括直接质谱注入法（鸟枪法）、色谱质谱联用法和核磁共振法等。脂质组学在疾病早期诊断、生物标志物的发现、新药研发以及系统研究方面都发挥了很大作用。本文旨在介绍脂质组学在疾病生物标志物发现中的应用及其研究方法。     

基于脂质组学技术发现冠心病的脂质标志物和治疗靶点

冠心病是全球第一的死亡原因,其主要特征是冠状动脉粥样硬化使管腔狭窄或闭塞导致心肌缺血、缺氧或坏死而引发的心脏病,冠心病与脂质调节异常、慢性炎症、内皮功能障碍等密切相关。目前用于诊断冠心病的心肌酶和高、低密度脂蛋白等只能部分解释冠心病的风险。尚不能有效地检测冠心病患者早期的高危因素,迫切需要新的技术发现与冠心病密切相关的疾病标志物。脂质分子是心肌细胞结构重要组成部分,在心脏功能方面扮演重要角色。脂质组学是高通量研究脂质组成的一门新兴学科。近年脂质组学研究显示,特定种类的脂类,如神经酰胺、鞘氨醇、溶血磷脂酸、氧化脂质等,与冠心病的临床分型及特征相关。此外动物模型中心脏、脂肪、肝脏等相关组织样本脂质组学研究成果也为脂质生物标志物提供了新的信息,脂质组学技术正越来越多地被用于评估冠心病的风险等相关研究。本文对利用脂质组学技术探究冠心病脂质小分子标志物以及相关治疗靶点、药物研发策略进行综述。     

内质网脂质稳态在细胞色素P450酶调控中的作用

脂质是机体内重要的营养物质之一,参与机体的能量供应、生物膜形成以及代谢调节等,内质网是其合成的主要场所。近年来越来越多研究表明,细胞色素P450酶的表达和活性影响机体对有害物质的敏感性以及药物的疗效,影响疾病的发生及发展,而细胞色素P450酶作为膜蛋白受到膜组成的影响。就细胞色素P450酶调控过程中内质网脂质稳态的作用进行综述。     

代谢组学在代谢性疾病研究中的进展

现代社会人们的饮食、营养结构和生活方式发生了巨大改变,高血压、高血脂/动脉粥样硬化、糖尿病及肿瘤等代谢性疾病发病率日趋升高,严重地危害了人类健康。虽然研究发现代谢性疾病均与生化代谢紊乱密切相关,但这些疾病发病过程和机理一直不甚明了。代谢组学通过定量检测体内小分子化合物水平研究机体基础代谢的变化,可为探索代谢性疾病的发病过程和发病病理提供直接数据。近年来利用代谢组学技术对多种代谢性疾病的研究取得了一定的进展。研究发现这些疾病发生过程中机体生化代谢发生了明显变化,主要涉及能量代谢、氨基酸代谢、脂代谢等。另外高血压、高血脂和糖尿病之间还呈现相互关联、互为因果的关系,在其相互引发过程中,脂肪酸的代谢可能是一个重要的桥梁,氧化应激、胰岛素抵抗和交感神经的兴奋等相互影响的因素也起着重要作用,导致单一的代谢性疾病发展成各种疾病并存状态。本文从代谢组学研究生化代谢变化的角度综述了近年来代谢性疾病研究的进展,旨在阐述众多代谢性疾病与代谢紊乱的相互关联,为预防和治疗代谢性疾病提供新的思路和对策。     

基于代谢组学技术探讨高尿酸血症合并慢性肾脏疾病的研究进展

摘要：代谢组学具有灵敏、快速、高通量的特点,在研究内源性小分子的变化规律、发现异常代谢物、揭示个体代谢表征等方面具有应用潜力。利用代谢组学研究高尿酸血症合并慢性肾脏疾病是近年来的热点。对高尿酸血症合并慢性肾脏疾病的相关代谢组学的研究表明,该病与氨基酸、脂质代谢紊乱密切相关。就代谢组学在高尿酸血症合并慢性肾脏疾病发病机制探索、生物标志物筛选、中药治疗方面的应用展开综述。     

不同价态锰对小鼠体内脂质过氧化的影响

锰是动植物营养所必需 ,也是人体代谢过程中不可缺少的一种微量元素。实验证明 ,锰与机体的若干重要物质代谢有密切关系 ,适量的锰可增强蛋白质代谢 ,影响糖代谢中若干酶的作用。但是过量锰暴露可以导致锰毒性反应 ,且低价锰的毒性高于高价锰。有研究结果表明锰对神经系统和肝脏具有较大的毒性 ,可引起体内脂质过氧化的改变等[1 ,2 ] ,但不同价态的锰对机体的毒作用的研究报道甚少 ,本研究通过测定肝及脑组织中ＭＤＡ含量及全血ＳＯＤ活性等指标 ,初步探讨不同价态的锰对机体脂质过氧化和抗氧化系统的影响。1　材料与方法1 1　试剂　氯化锰 …     

以蛋白翻译后修饰的视角探究脂肪肝的发病机制

脂肪肝是如今全世界的人所面临的最严重的健康问题之一,可分为酒精性脂肪和非酒精性脂肪肝。为了治疗脂肪肝,调节机体内脂质的代谢过程成了其中一个重要的方向。其中,通过影响与脂质代谢有关的蛋白质的活性和水平来降低肝脏内部脂质含量,是主要的目标之一。除去基因水平的调控对蛋白质的影响,蛋白翻译后修饰也是备受重视,本篇综述主要是对与脂代谢相关的蛋白质的翻译后修饰进行介绍。     

基于脂质组学技术的中药降脂作用研究

高脂血症是一种常见的血脂异常疾病,是导致各种心血管疾病的重要危险因素。中药具有疗效确切、不良反应少、作用温和等优点,广泛应用于预防和治疗高脂血症。然而,由于中药成分复杂且作用靶点多,其降脂作用机制尚不明确。脂质组学作为研究生物系统中脂质及脂质相互作用的一门学科,能对不同生理病理状态下的脂质进行定性定量分析,寻找与中药降脂作用相关的潜在生物标志物,为系统地研究中药降脂作用提供可借鉴的思路。本综述介绍了脂质组学的主要研究方法,总结了近年来脂质组学在中药降脂作用研究中的应用,以期为中药降脂作用研究提供方法参考。     

代谢组学技术在临床诊断中的研究进展

代谢组学是系统生物学的重要组成部分。研究显示,代谢组学在临床诊断过程中有着不可比拟的作用。当机体受到外源性或内源性刺激时,体内小分子代谢物的种类及含量会发生显著改变,代谢组学技术通过对体内复杂代谢物的动态变化进行分析,分析代谢物变化与机体病理或生理变化的直接相关性。随着分析技术的不断发展,核磁共振、色谱-质谱联用等先进技术被广泛应用于代谢组学的研究中。目前临床运用代谢组学技术可以全面分析患者体液中代谢物的动态变化,发现体液中与疾病密切相关的特征性生物标志物,从而实现疾病的早期临床诊断。本文主要对代谢组学技术及其在临床诊断过程中的广泛应用作一综述。     

用于治疗2型糖尿病的中药及其代谢组学研究

糖尿病(Diabetes mellitus,DM)作为最具代表性的代谢性疾病,是一组与胰岛素作用异常相关、以血糖增高为特点的慢性疾病群,并且大多数是2型糖尿病(T2DM)。代谢组学通过对其最终代谢产物进行系统分析,揭示机体整体的生理和病理状态,探讨药物治疗疾病的作用机制。本文通过对近年来中医药应用于T2DM的研究进行文献综述,包括常用中药处方、中成药、药膳、中医药治疗糖尿病的代谢组学等,为中医药进一步应用于2型糖尿病的治疗研究提供科学依据。     

RNA N6-腺苷酸甲基化修饰在慢性肝病中作用的研究进展

N⁶-腺苷酸甲基化(m⁶A)修饰是病毒和真核生物RNA最丰富、最重要的内部修饰,在基因的转录后调控中起关键作用。m⁶A修饰调控RNA生命过程的各个方面,包括加工、输运、翻译和降解。肝是病理生理过程中重要的代谢和消化器官。最近研究表明,m⁶A修饰对肝功能和肝病的发展具有显著的调节作用。本文主要综述m⁶A修饰在慢性肝病如病毒性肝炎、肝纤维化、非酒精性脂肪性肝病和肝癌等中的生物学和临床意义,为慢性肝病的治疗提供参考。     

Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.     

Nuclear receptor regulation of lipid metabolism: potential therapeutics for dyslipidemia, diabetes, and chronic heart and liver diseases

Lipids are essential components of biological membranes, fuel molecules and metabolic regulators that control cellular functions, metabolism and homeostasis. The liver plays a central role in regulating lipid metabolism and whole body lipid homeostasis. Sterols, bile acids and fatty acids are the endogenous ligands of the liver orphan receptor, farnesoid X receptor, peroxisome proliferator-activated receptor, vitamin D receptor, constitutive androstane receptor and pregnane X receptor. These metabolic receptors coordinately regulate lipid, glucose, energy and drug metabolism. Alteration of lipid homeostasis causes dyslipidemia, which is a major risk factor contributing to atherosclerotic cardiovascular diseases, diabetes, obesity and liver diseases. Advances in the understanding of the mechanisms of nuclear receptor regulation of lipid homeostasis have provided an opportunity to investigate potential therapeutic drugs targeted to nuclear receptors. This could be useful for the treatment of diabetes, and cardiovascular and chronic liver diseases.     

活血化瘀中药在纤维化肝病中的作用

在慢性肝病的治疗中,抗纤维化的治疗是非常重要的一个方面,也是治疗中的难点。能否阻断肝纤维化的形成与发展,对阻止或延缓慢性肝病向肝硬化的转变具有重要意义。肝纤维化为诸多慢性肝病发展至肝硬化过程中所共有的病理组织学变化,是影响慢性肝病预后的重要环节,减缓或阻止肝纤维化进程是一相当重要的治疗对策,中医药主要选用活血化瘀的药物,以降解纤维组织。活血化瘀药物具有消除淤血、通行血脉、促进血行等作用,随着对活血祛瘀药的研究,将对肝纤维化的治疗开辟新的领域。     

细胞焦亡在肝病中的作用及中医药治疗的研究进展

细胞焦亡是一种与炎症相关的新型程序性细胞死亡,其发生与炎症小体密不可分,作为天然免疫系统的组成部分,是机体受到异常刺激后免疫系统清除有害因子进行组织修复而产生的防御反应。炎症反应可以提高机体清除损伤因子的能力,但过度活化则可能会对机体造成损害。随着研究逐步深入,细胞焦亡被认为与肝脏疾病的发生、发展密切相关。中医防治肝脏疾病由来已久,在临床中已经取得良好的疗效。研究显示,中药通过调控细胞焦亡相关通路蛋白与炎症因子,从而干预疾病的进展。现结合现代医学,对细胞焦亡在肝脏疾病中的作用机制进行归纳与总结,并对现阶段的中医治疗进展加以阐述。     

老年人非酒精性脂肪性肝病与血脂血糖水平及体重指数的关系

目的探讨老年人非酒精性脂肪性肝病(NAFLD)与血脂血糖水平、体重指数等指标的关系。方法298例老年人按非酒精性脂肪性肝病诊断标准分为脂肪肝组(114例)和非脂肪肝组(184例),观察临床表现,检测血脂、血糖、体重指数、肝功能等指标并进行分析。结果脂肪肝组血脂、血糖水平、体重指数明显增高,和非脂肪肝组比较差异有显著性(P相似文献   

Dyslipidemia in northeastern China

Dyslipidemia, is a major risk factor for premature coronary artery disease. Our aim was to estimate the prevalence of dyslipidemia (blood lipid abnormalities) and other risk factors associated with coronary artery diseases among an adult population in northeastern China. Throughout the months of September and October of 2007,a population-based cross-sectional study was conducted and a total of 3,815 individuals were included. Total cholesterol (TC), high-density cholesterol (HDL-C), low-density cholesterol (LDL-C), and triglycerides (TG) were measured. A binary logistic regression analysis was conducted to determine risk factors associated with dyslipidemia. The prevalence of hypercholesterolemia, high LDL-C, low HDL-C, and hypertriglyceridemia were 17.3%, 27.8%, 11.66% and 29.85%, respectively. The prevalence of hypertension, central obesity, alcoholic liver disease (ALD), non-ALD, diabetes and metabolic syndrome was higher in serum lipid abnormality groups than in the non-dyslipidemia group (p < 0.001). In a binary logistic regression, hyperlipidemia was positively correlated with age, male, hypertension, high body mass index, etc. There were negative correlations with being female and the level of education a subject had attained. Dyslipidemia is a major risk factor for premature coronary artery diseases and an important public health issue in the northeastern part of China. Dyslipidemia is more frequent than expected based on previous studies. To control dyslipidemia, routine evaluations in clinics and community centers are needed, as well as effective public health education.     

酒精性脂肪肝脂质代谢研究进展

酒精性脂肪肝(AFL)是长期大量饮用酒精引发的肝脏损害性病变,可逆转也可进一步发展为肝纤维化和肝硬化。众多的脂肪细胞因子如瘦素(Leptin)、抵抗素(Resistin)和肿瘤坏死因子-α(TNF-α)在脂肪肝的发病中起到一定的促进作用,脂联素(Adiponectin)能改善脂质代谢,延缓脂肪肝的发生;脂联素通过腺苷酸活化蛋白激酶(AMPK)调节糖脂代谢、改善胰岛素敏感性。脂联素/AMPK信号通路是酒精在肝脏的作用靶点、也是调节PPARγ作用的重要信号通路;脂肪分化相关蛋白(ADRP)调节脂质代谢、促进酒精性脂肪肝的形成;过氧化物酶增殖体激活受体γ(PPARγ)参与机体脂质稳态的调节,脂肪肝时PPARγ表达增高,肝纤维化时PPARγ表达减少。对酒精性脂肪肝脂质代谢的深入研究,有助于阐明酒精性脂肪肝发病机制并为临床防治ALD及脂质代谢相关疾病提供新策略。     

Puerariae flos alleviates metabolic diseases in Western diet-loaded, spontaneously obese type 2 diabetic model mice

Puerariae flos extract (PFE) has been reported to have many effects, including preventing the development of hangovers, liver protective effects, and an estrogenic effect. In addition, some papers reported that PFE is effective against metabolic diseases, with hypolipidemic and hypoglycemic effects. However, the mechanism underlying such effects remains unclear. For the purpose of clarifying the effect of PFE on metabolic diseases related to the accumulation of visceral fat and to determine the mechanism of such action, TSOD mice, a multifactorial genetic disease animal model that spontaneously develops various metabolic diseases such as obesity and type 2 diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD-WTD). When TSOD mice were loaded with WTD, it was confirmed that metabolic diseases such as obesity and abnormal glucose/lipid metabolism are aggravated. In contrast, PFE treatment to TSOD-WTD mice was shown to suppress body weight gain and visceral fat accumulation, alleviated the abnormal glucose tolerance and hyperinsulinemia, as well as causing an increase in blood adiponectin. Furthermore, the suppression of liver enlargement was observed in PFE-treated mice, with suppression of fatty degeneration and anti-inflammatory effect. In addition, to clarify the mechanism of the hyperlipidemia-alleviating effects in the liver, we investigated the effect of PFE on the expression of genes involved in cholesterol homeostasis. PFE was associated with a significant increase in gene expression for cholesterol synthesis rate-limiting enzyme HMG-CoA reductase, cholesterol catabolization enzyme Cyp7A1, bile salt export pump adenosine triphosphate-binding cassette transporter B11, and low-density lipoprotein receptor involved in cholesterol uptake. The above results suggest that PFE acts to alleviate the effects of various metabolic diseases based on the accumulation of visceral adipose tissue, including obesity, diabetes, and hyperlipidemia, with the promotion of catabolization/excretion of cholesterol in the liver being a key mechanism of action.     

Deciphering the toxicological role of Porphyromonas gingivalis derived endotoxins in liver diseases

Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues. Porphyromonas gingivalis, a Gram‑negative oral anaerobe, mainly causes periodontitis and it is one of the most important risk factors responsible for aggravation of existing systemic diseases. Several experimental and clinical studies have shown the positive association between periodontitis and different forms of liver disease. Periodontal diseases increase the prevalence of non-alcoholic fatty liver diseases and cirrhosis. Infected periodontium and pathogens in the periodontal microenvironments release pathogen-associated molecular patterns such as peptidoglycan, lipopolysaccharides, gingipain, fimbria, bacterial DNA, etc, and damage-associated molecular patterns such as interleukins-1α, β, − 8, and galectin-3, etc. These virulence factors and cytokines enter the bloodstream, disseminate into the whole body, and induce a variety of systemic pathological effects, including liver diseases (steatosis and fibrosis). Maintaining oral hygiene by scaling and root planning significantly improves liver damage in patients with periodontitis. Dentists and physicians should have more awareness in understanding the bidirectional nature of the relationship between oral and systemic diseases. Importantly, periodontitis condition aggravates simple fatty liver into fibrotic disease and therefore, the aim of this review is to understand the possible link between periodontitis and liver diseases.