叶酸在心脑血管疾病防治中的机遇与挑战

叶酸缺乏可导致高同型半胱氨酸血症,而高同型半胱氨酸血症是心脑血管疾病的独立危险因素。过去认为补充叶酸可降低体内同型半胱氨酸水平,从而预防心脑血管疾病的发生。但随着大量临床随机对照试验的进行,人们发现降低同型半胱氨酸血症并不能为心血管疾病患者带来益处,脑卒中方面的益处还需要更多临床数据证明。叶酸等B族维生素在心脑血管疾病的预防领域还存在着很大的挑战。笔者就目前叶酸等在心脑血管疾病中的应用现状及存在问题作一综述。     

叶酸在妊娠期的应用研究进展

叶酸是参与人体代谢的重要的微量营养素之一,对妊娠妇女及胎儿、新生儿健康有非常重要的意义。本文重在研究叶酸在妊娠期的作用及其机制,从而从妊娠期妇女及胎儿叶酸缺乏症的预防及叶酸补充角度对叶酸在妊娠期的重要作用做出概述。     

国内外医药信息集粹

1.中美共同完成的“补充叶酸预防脑卒中”研究获高度评价。 近日,由中美科学家共同完成并发表于权威医学期刊《柳叶刀》上的学术研究论文《补充叶酸预防脑卒中的疗效：一项荟粹分析》一文，赢得国际权威机构“千名医学家”（Faculty of 1000 medicine）的科学文献贡献力高度评价,被推荐为必读文章,评价得分在最近半年的脑卒中研究论文中排名第一。     

叶酸干预治疗对H型高血压患者血浆同型半胱氨酸血压水平及主要心脑血管事件的影响

<正>据相关调查显示,我国高血压患者数量正呈逐年上升的趋势,高血压是脑卒中、冠心病、糖尿病等疾病重要的危险因素,血压水平与心脑血管疾病的发病风险呈正相关。同型半胱氨酸(Hcy)是体内蛋氨酸代谢途径中的中间产物,在叶酸的作用下可重新合成蛋氨酸,叶酸缺乏时,Hcy代谢受阻就会使血液中浓度增加。当人体血浆中的Hcy水平在10μmol/L以上时称为高Hcy     

社区宣教对外来育龄女工叶酸认知度的影响

叶酸是人体必需的B族维生素,体内缺乏叶酸会引起多种疾病,尤其是育龄女性叶酸缺乏会使新生儿畸形尤其是神经管畸形的发病率升高[1]。本组资料主要采用问卷调查的形式,对深圳市观澜街道外来育龄女工进行叶酸及出生缺陷相关知识的健康宣教,并对宣教前后叶酸知信行进行调查,力求找到更好的提高她们叶酸知信度的方法,减少本地区出生缺陷儿的发生。     

补充叶酸预防冠心病

叶酸是维生素B族大家庭中的一员,最初是从菠菜叶中提取而来,因此得名。虽然我们人体每天对叶酸的需要量不大。但是叶酸在体内的作用却是必不可少的。     

亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸与高血压合并缺血性脑卒中的相关性研究

<正>高血压合并缺血性脑卒中在临床中常被称作脑梗死,属于目前最为普遍的一种心脑血管类疾病,若患者出现高血压合并缺血性脑卒中,则其体内的亚甲基四氢叶酸还原酶(MTHFR)基因会表现出与健康人明显不同的多态性,且患者体内的血浆     

5,10-亚甲基四氢叶酸还原酶基因多态性与不育不孕症相关性研究进展

5,10-亚甲基四氢叶酸还原酶是叶酸代谢通路中的关键酶,在编码该酶的MTHFR基因中已发现多种单核苷酸多态性位点可能导致该酶活性的降低。该酶维持体内同型半胱氨酸正常水平及参与DNA的合成。MTHFR基因多态性被发现可能与男性不育及育龄女性复发性流产有关,将可能导致体内高同型半胱氨酸水平和DNA合成障碍及低甲基化反应,使人体叶酸代谢发生障碍。本文就5,10-亚甲基四氢叶酸还原酶基因多态性对男性不育、育龄女性复发性流产的影响进行综述。     

补充叶酸对结、直肠癌发生的双面影响

叶酸在DNA的合成和复制中起着重要作用,原有研究提示补充叶酸可以降低罹患结、直肠癌的风险,但近年来的研究对此提出了异议。本文通过相关文献复习发现,补充叶酸虽可在人体未形成结、直肠癌之前通过提高DNA甲基化的稳定性而产生预防肿瘤的作用,但当肠道内已形成肿瘤微小病灶后,补充叶酸反能产生促进肿瘤生长的作用,这可能与叶酸会促进肿瘤细胞的增殖有关。此外,补充叶酸对预防结、直肠癌的有效性有时间和剂量依赖性。因此,在应用叶酸预防结、直肠癌前应常规使用结肠镜进行肿瘤筛查,以排除早期微小腺瘤。有条件的还应进行红细胞及乙状结肠上皮内的叶酸浓度测定,以评估患者的叶酸水平并据此避免补充的叶酸剂量过大。叶酸水平与罹患结、直肠癌的关系仍有待学者们更深入研究的揭示。     

正确使用叶酸

叶酸是人体内细胞生长和繁殖所必需的物质,对人体的新陈代谢起着重要作用,是人体不可缺少的营养元素之一。妊娠期妇女合理补充适量的叶酸可以明显降低胎儿发生神经管畸形的危险性,适当补充叶酸也可以有效预防和降低巨幼红细胞贫血、抑郁症、高血压病、肿瘤和冠状动脉粥样硬化性心脏病等疾病的发生率。     

Blood-Brain Barrier Transport of Reduced Folic Acid

Purpose. The brain is relatively resistant to folic acid deficiency, indicating specialized transport systems may exist for this vitamin localized within the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. The present studies quantify the BBB transport of [³H]-methyltetrahydrofolic acid (MTFA) in vivo and in isolated human brain capillaries in vitro. Methods. BBB transport of [³H]-MTFA was compared to that of [¹⁴C]-sucrose, a plasma volume marker, following either intravenous injection or intracarotid perfusion in anesthetized rats. Competition by 10 M MTFA or 10 M folic acid was examined to determine whether folic acid is also transported by the MTFA uptake system. Results. The BBB permeability-surface area (PS) product of [³H]-MTFA, 1.1± 0.3 L/min/g, was 6-fold greater than that of [¹⁴C]-sucrose following intravenous injection. The BBB PS product determined by intracarotid arterial perfusion was not significantly different from the BBB PS product calculated following intravenous injection. A time- and temperature- dependent uptake of [³H]-MTFA in human brain capillaries was observed. The uptake of [³H]-MTFA by either rat brain in vivo or by human brain capillaries in vitro was equally inhibited by 10 M concentrations of either unlabeled MTFA or unlabeled folic acid. Conclusions. (1) A saturable transport system exists at the BBB for folic acid derivatives and since this transport is equally inhibited by either folic acid or MTFA, it is inferred that this transport system is the folic acid receptor, and not the reduced folic acid carrier. (2) The presence of a folate transport system at the BBB may offer an endogenous transport system for brain drug delivery of conjugates of folates and drugs that do not normally cross the BBB in vivo.     

补充叶酸和复合维生素B降低脑卒中患者复发的研究

目的:探讨叶酸和复合维生素B(VitB)对血浆同型半胱氨酸(Hcy)及脑卒中的作用.方法:134例脑卒中患者依随机数字表法分为叶酸和复合VitB治疗的干预组和常规治疗的对照组各67例,分别检测各组患者人院和出院时血浆Hcy、D-二聚体(D-D)、纤维蛋白原(FIB)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平,观察干预效果.随访12个月,运用脑卒中残损评定法(SIAS)进行评价,确定患者预后情况.结果:干预后干预组血浆Hcy水平为(13.59±3.84)μmol/L,对照组为(14.78±4.32) μmol/L,均较干预前有所下降,差异有统计学意义(均P＜ 0.01).干预组D-D、TC、TG、LDL-C和FIB水平治疗后均下降,治疗效果优于对照组,差异有统计学意义(P＜ 0.05或P＜0.01).干预组脑卒中患者复发率(22.4％)低于对照组(44.1％).前者SIAS评分为(20.72±2.33)分,明显高于后者的(12.70±1.77)分,差异有统计学意义(P＜0.01).结论:补充叶酸和复合VitB可降低血浆Hcv水平,对预防和治疗脑卒中具有重要意义.     

Folic Acid improves baroreceptor sensitivity in hypertension

In hypertension baroreceptor-mediated modulation of heart rate is impaired, resulting in a decreased vagal control. Reactive oxygen species produced locally in the vasculature decrease baroreceptor sensitivity. Folic acid has antioxidant properties. Therefore, the aim of this study was to test whether folic acid improves baroreceptor function in hypertension. Twenty-one male patients with hypertension not taking any drugs for 2 weeks participated in the study and were randomized to folic acid 5 mg or matching placebo. Cardiac and vascular sympathetic baroreceptor functions were tested before and after a single dose of folic acid or placebo with two different methods: the alpha-coefficient method and the phenylephrine (PE) and sodium nitroprusside (SNP) bolus method. In the folic acid group both methods showed significantly improved cardiac and vascular sympathetic baroreceptor sensitivity compared with placebo. This study provides evidence that folic acid improves cardiac and vascular sympathetic baroreceptor sensitivity in hypertensive patients, which suggests an improved vagal control and an enhanced baroreceptor modulation of sympathetic vasomotor tone. Thus, folic acid may represent a novel treatment for prevention of orthostatic dysregulation and/or arrhythmic complications resulting from baroreceptor dysfunction.     

马来酸依那普利叶酸片预防H型高血压脑卒中的价值

目的探讨马来酸依普那利叶酸片在预防H型高血压患者并发脑卒中及降低血浆同型半胱氨酸(Hcy)水平中的临床价值。方法将所选H型高血压患者分为依那普利组和依那普利叶酸片组,于入选时测定血浆同型半胱氨酸水平,治疗后1个月、6个月分别复测血浆同型半胱氨酸水平,并观察6个月后各组脑卒中发生情况。结果依那普利叶酸组血浆同型半胱氨酸水平及脑卒中发生率显著低于依那普利组(P<0.05)。结论马来酸依那普利叶酸片能有效地降低H型高血压患者血浆同型半胱氨酸(Hcy)水平及脑卒中发生率。     

叶酸与消化系统疾病

叶酸是一种生长因子 ,其缺乏会出现机体多系统受损。在消化系统中可发生慢性萎缩性胃炎、结肠炎 ,甚至会增加患消化道肿瘤的危险。而且叶酸缺乏与肝细胞受损及巨幼红细胞性贫血密切相关。本文就叶酸的来源、代谢、生理功能、与消化系统疾病中的关系、实验室检测及其机体需要量的探讨作一综述。     

HPLC法测定保健食品中的叶酸

目的建立HPLC法测定保健食品中叶酸含量的方法。方法采用Phenomenex Gemini C18色谱柱,柱温：25℃,流动相：乙腈-0.05mol.L-1磷酸二氢钾溶液,检测波长：280nm。结果叶酸在0.02094~1.047μg范围内线性良好,r=0.99997,平均回收率为99.97%,RSD为1.87%（n=9）。结论该法准确可靠,为保健食品中叶酸的测定提供了方法 。     

围孕期妇女补充叶酸预防神经管畸形的效果分析

目的:探讨围孕期妇女补充叶酸预防神经管畸形的效果。方法:对2004年1月至2013年9月在我院建档、检查的围孕期妇女的资料进行回顾性分析和总结,分别将不同时间段分娩的围产儿及神经管畸形儿作为对照组(2004—2008年)和观察组(2009年至2013年9月),通过对两组资料进行分析比较,了解孕期妇女补充叶酸预防神经管畸形的效果。结果:对照组发生神经管畸形9例,观察组发生2例,两组比较差异具有统计学意义(P<0.05)。结论:围孕期妇女补充小剂量叶酸是预防神经管畸形的重要手段,可有效降低胎儿神经管畸形的发生率;应对育龄妇女加强服用叶酸的宣教。     

妊娠妇女在不同孕期血清铁蛋白、叶酸和维生素B_(12)的检测及临床意义

目的检测妇女妊娠期血清铁蛋白、叶酸和维生素B12的含量,为预防和治疗妊娠贫血提供实验依据。方法用化学发光免疫分析方法检测妊娠妇女血清铁蛋白、叶酸和维生素B12的含量。结果血清铁蛋白、叶酸和维生素B12的含量随孕期增长而降低,早孕妇女与正常对照组比较,铁蛋白和叶酸明显低于对照组(P<0.05),维生素B12无统计学意义(P>0.05);中、晚孕期妇女血清铁蛋白、叶酸和维生素B12的含量与正常对照组比较,铁蛋白、叶酸和维生素B12均显著低于对照组(P<0.01)。结论测定妇女妊娠期血清铁蛋白、叶酸和维生素B12的含量,可以鉴别妇女妊娠期贫血的原因,预防和治疗孕妇贫血,并保障胎儿的正常生长发育。     

Folic Acid Targeting of Protein Conjugates into Ascites Tumour Cells from Ovarian Cancer Patients

Abstract

Despite a wealth of in vitro data describing the use of folic acid for drug and DNA delivery into ovarian cancer cell lines, there have been no reports describing the targeting of such compounds to freshly isolated tumour cells. We have carried out a study to determine the usefulness of folic acid as a targeting ligand for ovarian cancer by measuring the uptake of folic acid—BSA-FITC in tumour cells isolated from the ascitic fluid of ovarian cancer patients. In 7 out of 7 patients we have found folic acid mediated uptake of the fluorescently labelled albumin, with the accumulation (average cell fluorescence) and differential uptake (ratio between receptor mediated and fluid phase uptake) varying between patients. Accumulation of folic acid—albumin-FITC occurs in ascites tumour cells expressing the epithelial cell marker EMA, with a significant proportion of EMA negative cells also accumulating the conjugate. There is no correlation between cell cycle and uptake of folic acid-BSA-FITC. These results suggest that folic acid-targeting of therapeutics is a promising approach for the treatment of ovarian cancer.     

Folic acid and human malformations: a summary and evaluation

A large body of evidence gathered over the past 30 or more years has led to the firmly established belief that deficiency of the vitamin folic acid is a cause of congenital malformations of neural tube closure. Beginning with studies showing folic acid levels of mothers of children with such defects to be low, this belief has been solidified by epidemiologic studies revealing that this consequence is prevented by maternal supplements of the vitamin from early pregnancy. The present article reviews this evidence for the purpose of examining the claims of the efficacy of folic acid in this respect. This seems to be an advantageous moment to do so, because no clear impact of folic acid supplementation and fortification on the prevalence of neural tube defects has as yet been documented; and furthermore a pause seems to have been reached in such studies. It is felt that a historical, i.e. a chronologic approach will best describe the findings, and therefore they will be considered as they unfolded.