血脂异常相关酶的研究进展

血脂异常在临床上最常见的是高脂蛋白血症。随着经济的发展和人民生活水平的提高,高脂血症作为心脑血管疾病的重要危险因素,更加威胁着人类健康,对脂质异常和相关酶的研究也在逐渐深入。本文综述了几种与脂质代谢异常相关的关键酶及其研究进展。     

低氧对脂肪细胞发育及脂质代谢调控研究进展

脂肪细胞的生长、分化与增殖贯穿整个生命过程,脂肪细胞中脂质代谢紊乱影响脂肪组织免疫和全身能量代谢。脂质代谢参与调控机体多种疾病的发生与发展,如高脂血症、非酒精性脂肪肝病、糖尿病和癌症等,对人和动物健康具有重大威胁。低氧诱导因子（hypoxia inducible factor,HIF）是介导机体组织器官中氧感受器的主要转录因子,HIF可调控脂质合成、脂肪酸代谢和脂滴形成并诱导疾病发生。但由于低氧程度、时间和作用方式的不同,对机体脂肪细胞发育和脂质代谢产生有害或有益的影响还无从定论。本文总结了低氧介导转录因子的调控作用以及对脂肪细胞发育和脂质代谢调控的研究进展,旨在揭示低氧诱导脂肪细胞代谢途径变化的潜在机制。     

铁死亡及其在心脑血管疾病中的研究进展

铁死亡是一种程序性细胞死亡方式,其发生伴随铁依赖性脂质活性氧的积累和质膜多不饱和脂肪酸的消耗,涉及脂质代谢、氨基酸代谢和铁代谢三个过程。心脑血管疾病严重危害人类健康,是心脏血管和脑血管疾病的综合,铁死亡在其发病过程中发挥了至关重要的作用。现主要围绕铁死亡的机制及其在心脏血管和脑血管疾病中的影响等相关问题进行综述,从而为相关疾病的防治提供参考。     

传统大豆发酵食品在心脑血管疾病防治上的研究现状

人类生活水平的提高以及生活压力的增加,使心脑血管疾病的发生频率显著增加,并日趋成为威胁人类健康的重要原因。传统大豆发酵食品中的各种生理活性物质通过降血压和调节体内脂质、糖类代谢等多种作用来有效地防治心脑血管疾病;与传统药物相比,有效果显著与无毒副作用等优点,因此传统大豆发酵食品有广阔的发展应用前景。     

复方银杏通脉胶囊的制备及质量标准研究

据文献报道,银杏叶提取物对中枢β-肾上腺素系统及脂质代谢有改善作用,能扩张冠状动脉和脑动脉,改善心脑血管和周围血管循环功能,增加心脑血流量,促进心脑细胞代谢,降低心肌耗氧量,对心肌缺血引起的心功能紊乱有改善作用。主要应用于治疗心脑血管疾病和老年性痴呆。对冠心病,心     

青龙胶丸对高脂血症患者血液脂质代谢改变的干扰作用

本文观察了１５列高脂血症患者血液脂质代谢改变,结果与１５例健康对照组比较,发现高脂血症病人ＨＤＬ—ｃｈ、ＡＰＯＡ—Ⅰ降低,ＡＰＯＢ含量增加。口服青龙肠溶胶九的高脂血症患者ＡＰＯＡ—Ⅰ增加。ＡＰＯＢ、ＴＣ、ＴＧ下降,血液粘滞度降低,提示青龙胶丸具有改善脂质代谢失衡、降低血脂和血粘度作用。     

高脂血症的合理治疗

血脂即血中所含脂质的总称,其中主要包括胆固醇(TC)、甘油三酯(TG)、磷脂和脂肪酸。由于脂质代谢或运转异常使血浆中一种或几种脂质高于正常称为高脂血症,可表现为高胆固醇血症、高甘油三酯血症或两者兼有(混合型高脂血症)。脂质不溶于水或微溶于水,必须与载脂蛋白结合以脂蛋白形式存在,才能在血液循环中运转,因此高脂血症常为高脂蛋白血症的反映。     

食源性黄酮类化合物改善脂质代谢作用及其机制研究进展

黄酮类化合物是广泛存在于自然界中的一类多酚类化合物,已被研究证实具有十分广泛的生物活性。近年来,大量研究表明,黄酮类化合物对脂质代谢紊乱具有改善作用,对高脂血症及相关疾病亦有一定的预防和治疗作用。目前认为,黄酮类化合物改善脂质代谢的作用机制主要是通过调节机体对肠道中脂质的吸收和肝脏内脂质代谢过程,其中,固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)、过氧化物酶体增殖物激活受体(peroxisome proliferators activated receptors,PPARs)以及肝脏X受体(liver X receptors,LXRs)这三类核转录因子在这一调控过程中发挥着至关重要的作用。该文综述了食源性黄酮类化合物改善脂质代谢作用及其作用机制,并对其中存在的相关问题进行了初步分析和展望。     

长链非编码RNA在脂质代谢中的作用

脂质代谢是人体三大代谢之一，在激素等信号分子的调控下，脂质代谢处于稳定平衡的状态。当稳态被打破，血液中甘油三酯（triglyceride，TG）、胆固醇等水平发生变化，最终引起动脉粥样硬化（atherosclerosis，AS）、肥胖等脂质代谢疾病。长链非编码RNA（long noncoding RNA，lncRNA）是一组不具备蛋白质编码能力，长度大于200个核苷酸的RNA，近来研究发现，lncRNA与机体代谢、炎症和免疫系统以及血管功能的调控密切相关。大量文献表明，lncRNA参与脂质代谢调控，因而有望成为一些脂质代谢疾病的潜在治疗靶点。     

健康教育对心脑血管疾病终点事件发生的干预效应

通过健康教育干预探讨对心脑血管疾病发生之影响,为心脑血管疾病的防治工作提供理论依据。方法：从2000年到我院集中体检的大于50岁以上的在职和离退休干部4000人中,抽出资料完整并符合本次研究纳入标准者2000人,随机分为健康干预组和一般治疗对照组各1000人。其中干预组1000人中,高血压480人,高脂血症413人,高血压合并高脂血症107人;对照组1000人中,高血压478人,高脂血症423人．高血压合并高脂血症100人。两组均以高血压、高脂血症作为最主要的危险因素进行健康教育干预。健康教育干预组患者分别建立健康档案,制定系统的健康教育干预措施并组织实施,定期随访：一般治疗对照组患者将体检结果通知本人后,由其在门诊接受健康教育和治疗,对健康教育和治疗方法不作强制性规定。连续观察五年,比较两组五年间心脑血管疾病的发生情况（即以发生AMI／心绞痛、脑出血、脑血栓形成等心脑血管疾病的终点事件为评价标准）。结果：健康教育干预组病情控制良好,发生上述心脑血管疾病终点事件比危险因素对照组明显减少（急性心肌梗塞发生率为2．0％比3．4％,脑血栓发生率为4．3％比7．5％,TIA为2．1％比2．9％）,P〈0．01。结论：对存在心脑血管疾病危险因素者积极开展健康教育干预,可起到控制疾病进一步发展,减少心脑血管疾病终点事件的发生。     

脂蛋白脂酶调控因子研究进展

脂蛋白脂酶(Lipoprotein lipase, LPL)是脂质代谢的关键酶, 其正常调控对于机体向组织提供脂质营养至关重要。作为LPL重要的调控因子, 糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Glycosylphosphatidylinositol- anchored high density lipoprotein-binding protein 1, GPIHBP1)能与LPL结合起脂解平台的作用, 并作为载体参与LPL向毛细血管内皮细胞的转运。另外, 近年来也鉴定出其他几个LPL活性调控因子, 包括microRNAs、A型重复排序蛋白相关受体(Sortilin-related receptor with A-type repeats, SorLA)和载脂蛋白(Apolipoproteins, apo)。这些LPL调控因子的成功鉴定, 有助于人们深入认识机体脂解代谢和乳糜微粒血症发生的内在机制。文章重点综述了LPL的调控因子GPIHBP1的研究进展, 同时也对其他几个调控因子的研究进展进行了讨论。     

Metabonomics Study of the Therapeutic Mechanism of Gynostemma pentaphyllum and Atorvastatin for Hyperlipidemia in Rats

Gynostemma pentaphyllum (GP) is widely used for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China, and atorvastatin is broadly used as an anti-hyperlipidemia drug. This research focuses on the plasma and liver metabolites in the following four groups of rats: control, a hyperlipidemia model, a hyperlipidemia model treated with GP and a hyperlipidemia model treated with atorvastatin. Using ¹H-NMR-based metabonomics, we elucidated the therapeutic mechanisms of GP and atorvastatin. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) plotting of the metabolic state and analysis of potential biomarkers in the plasma and liver correlated well with the results of biochemical assays. GP can effectively affect lipid metabolism, and it exerts its anti-hyperlipidemia effect by elevating the level of phosphatidylcholine and decreasing the level of trimethylamine N-oxide (TMAO). In contrast, atorvastatin affects hyperlipidemia mainly during lipid metabolism and protein metabolism in vivo.     

Apolipoprotein polymorphism is associated with pro-thrombotic profile in non-demented dyslipidemic subjects

Apolipoprotein gene polymorphism has an important role in lipid metabolism and in the development of cerebro- and cardio-vascular disease (CCVD), including dementia. Dyslipidemia and hemostatic abnormalities are key risk factors associated with athero-sclerotic events preceding CCVD. The aim of this study was to evaluate the possible relationships of various apolipoprotein-species with hemostatic parameters and cognitive function. Lipid profile, gene polymorphism, coagulation markers, and mini-mental state examination (MMSE) scores were assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers. Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate with lipid or coagulation profile. These data suggest that apoE and apoA5 variants have an effect on hemostatic parameters, but they neither influence nor predict cognitive performance in non-demented individuals.     

Impacts of high-sucrose diet on circadian rhythms in the small intestine of rats

Excessive sucrose intake, known as fructose toxicity, leads to fatty liver, hyperlipidemia, and metabolic syndrome. Circadian disorders also contribute to metabolic syndrome. Here, we investigated the effect of excessive sucrose intake on circadian rhythms of the small intestine, the main location of sucrose absorption, to elucidate a mechanism of sucrose-induced abnormal lipid metabolism. Male Wistar rats were fed control starch or high-sucrose diets for 4 weeks. High-sucrose diet-induced fatty liver and hypertriglyceridemia in rats. Amplitudes of PER1/2 expression oscillations in the small intestine were reduced by excessive sucrose, while gene expression of GLUT5 and gluconeogenic enzymes was enhanced. These changes would contribute to interfering in lipid homeostasis as well as adaptive responses to control fructose toxicity in rats.     

Recent developments in the treatment of atherosclerosis

Atherosclerosis is one of the most frequent causes of cardiac arrest. The major cause of this disease is high concentrations of lipid in the blood. Medicinal agents so far have been quite successful in the management of hyperlipidemia. Among the several widely used drugs, (fibrates, statins and niacin) statins are the most frequently prescribed in many forms of hyperlipidemia. Recently, statins have been found to produce serious toxicities, which are rare but can be potentially harmful and are noise concern for the immediate need to develop some new chemical entities in this category. This review is primarily concerned with recent developments in atherosclerotic drug discovery including novel inhibitors of cholesterol biosynthesis, cholesterol absorption inhibitors and antioxidants. The review also focuses on possible future targets including gene therapy.     

Lack of UCP1 stimulates fatty liver but mediates UCP1-independent action of beige fat to improve hyperlipidemia in Apoe knockout mice

Brown adipose tissue (BAT) plays a critical role in lipid metabolism and may protect from hyperlipidemia; however, its beneficial effect appears to depend on the ambient temperature of the environment. In this study, we investigated the effects of uncoupling protein 1 (UCP1) deficiency on lipid metabolism, including the pathophysiology of hyperlipidemia, in apolipoprotein E knockout (APOE-KO) mice at a normal (23 °C) and thermoneutral (30 °C) temperature. Unexpectedly, UCP1 deficiency caused improvements in hyperlipidemia, atherosclerosis, and glucose metabolism, regardless of an increase in hepatic lipid deposition, in Ucp1/Apoe double-knockout (DKO) mice fed a high-fat diet at 23 °C, with BAT hyperplasia and robust browning of inguinal white adipose tissue (IWAT) observed. Proteomics and gene expression analyses revealed significant increases in many proteins involved in energy metabolism and strong upregulation of brown/beige adipocyte-related genes and fatty acid metabolism-related genes in browned IWAT, suggesting an induction of beige fat formation and stimulation of lipid metabolism in DKO mice at 23 °C. Conversely, mRNA levels of fatty acid oxidation-related genes decreased in the liver of DKO mice. The favorable phenotypic changes were lost at 30 °C, with BAT whitening and disappearance of IWAT browning, while fatty liver further deteriorated in DKO mice compared with that in APOE-KO mice. Finally, longevity analysis revealed a significant lifespan extension of DKO mice compared with that of APOE-KO mice at 23 °C. Irrespective of the fundamental role of UCP1 thermogenesis, our results highlight the importance of beige fat for the improvement of hyperlipidemia and longevity under the atherogenic status at normal room temperature.     

Dietary soybean phosphatidylcholines lower lipidemia: mechanisms at the levels of intestine, endothelial cell, and hepato-biliary axis

The beneficial metabolic effects of dietary soybean lecithin on lipid metabolism are now more clearly established. The intestinal absorption of cholesterol is decreased by soybean phosphatidylcholine-enriched diet and results in a cholesterol-lowering effect. There is an enhancement of the cholesterol efflux by endothelial cells incubated with soybean phosphatidylcholines, and a stimulation of the reverse cholesterol transport by high density lipoprotein-phosphatidylcholines. As a result of all these processes, phosphatidylcholines provided by the soybean lecithin metabolism appear to be key molecules controlling the biodynamic exchanges of lipids. They regulate homeostasis of cholesterol and fatty acids by decreasing their synthesis and promoting cholesterol oxidation into bile salts. Finally, the outcome is the increase in bile secretion of these lipids and/or their metabolite forms. Such findings constitute promising goals in the field of nutritional effects of soybean lecithin in the treatment or prevention of hyperlipidemia and related atherosclerosis.     

Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis

Apolipoprotein (apo) B-100 is a key protein compound of plasma lipid metabolism. This protein, as a sole component of LDL particles, to a great extent controls the homeostasis of LDL cholesterol in the plasma. Therefore, this protein and its structural variants play an important role in development of hyperlipidemia and atherosclerosis. Intensive research into the structure and biological functions of apoB-100 has led to identification of its complete structure as well as the responsible binding sites. With the development of the methods of molecular biology, some structural variants of the apoB-100 protein that directly affect its binding properties have been described. These are mutations leading to amino acid substitution at positions 3500 (R3500Q and R3500W) and 3531 (R3531C) that have been shown to decrease the binding affinity of apoB-100 in vitro. However, only the former mutations have been unequivocally demonstrated to cause hyperlipidemia in vivo. This minireview is aimed to discuss the impact of apoB-100 and its structural variants on plasma lipid metabolism and development of hyperlipidemia.