孔雀鱼胚胎心血管发育的显微观察

心血管系统的组织分化研究是近年热点课题之一1.胚体透明且发育速度快的鱼类胚胎由于具备便于观察的特性2,正广泛用于脊椎动物造血系统的发生、血细胞生成、及血循环系统分化时序、调控因子等研究3-5.孔雀鱼(Poecilia reticulata Peters)是卵胎生(Ovoviviparity)鱼类的代表种,其卵子在雌鱼的泄殖腔内受精发育,长成鱼后再出生 ;同时孔雀鱼又是一种小型观赏鱼类,在实验室易于饲养,能不断提供实验用卵和胚胎。因此,在本实验室长期进行鱼类组织细胞培养的基础上6-11,制备孔雀鱼胚胎组织标本,并对早期胚胎及心血管系统进行了体外培养, 观察和比较了孔雀鱼胚胎心血管系统在体内、外的形成过程。       

抗肿瘤药物对小鼠早期胚胎发育的影响

表观遗传修饰在基因表达和克隆胚胎的早期发育方面有重要作用.表现遗传修饰至少发生在两个关键时期--配子形成期和植入前胚胎,如果在此期间发生异常,则会导致胚胎的死亡及出生后各种疾病的发生.其中DNA的甲基化是最重要的一种表观遗传修饰类型,DNA甲基化在哺乳动物发育过程中起关键作用.综述几种类型抗肿瘤药物作用机制——其使胚胎的DNA甲基化降低,引起转录活性降低,进而导致胚胎发育停滞.     

叉头框-c2基因在主动脉弓发育过程中的作用

为了研究叉头框-c2（Forkhead Box c2, Fox c2）基因在心血管发生和发育中的作用, 通过制作小鼠的Fox c2 基因无效突变,解析该基因缺失鼠主动脉弓的异常发育状况.纯合子胎鼠从12.5天胚胎(embryo, E)开始有宫内死亡;即使完成宫内发育过程,新生鼠出生24 h后也全部死亡.这些鼠全部表现出与人的先天性心血管发育缺陷相似的B型或C型主动脉弓离断.杂合子鼠发育正常.E10.5胚胎的原位杂交分析显示,Fox c2 mRNA在第三、第四和第六弓型动脉强烈表达,而第四弓型动脉在E10.5胚胎后逐渐消失.这些结果表明,在主动脉弓形成过程中,Fox c2基因产物是左第四弓形动脉广泛改建所必需.     

人胚胎干细胞培养体系的研究进展

人胚胎干细胞具有广泛的研究前景,建立一个理想的人胚胎干细胞培养系统是利用它的前提.较详细地对目前关于人胚胎干细胞培养体系的研究进展、一些细胞因子对人胚胎干细胞的作用和影响以及体外长期培养对人胚胎干细胞核型的影响进行了综述.     

乙醇干扰斑马鱼胚胎发育中底索和背主动脉的形成

人类胚胎期乙醇暴露对心血管系统有严重致畸作用. 用不同浓度的乙醇处理斑马鱼胚胎, 发现能够干扰其胚胎循环系统的建立, 半数有效浓度(EC50)为182.5 mmol/L. 乙醇短暂暴露实验显示圆顶期为敏感时间窗, 400 mmol/L乙醇短暂暴露3 h能够导致43%的胚胎产生循环障碍. 我们排除了乙醇对斑马鱼造血系统影响, 通过血管内皮细胞分子标记(Flk-1)进行原位杂交显示, 乙醇干扰了躯干部体轴血管的建立, 而对头面部血管没有影响. 用动脉和静脉的分子标记(ephrinB2和ephB4)进行原位杂交以及半薄切片显示, 乙醇主要干扰斑马鱼背主动脉的形成, 而对体轴静脉没有明显影响. 进一步研究表明, 乙醇影响斑马鱼底索的发育, 因缺少底索分泌的Radar和Ang-1等血管形成因子, 间接地影响了背主动脉的形成和稳定. 这些结果为研究乙醇对人类心血管系统发育的影响提供了线索.     

钙网蛋白在心肌肥大中的研究进展

钙网蛋白(calreticulin, CRT)是内质网中主要的Ca2+结合分子伴侣,具有调控细胞Ca2+稳态、蛋白质合成与修饰等作用,参与调节细胞凋亡、应激、心血管炎症反应等多种生理和病理生理过程.CRT属于心脏胚胎基因家族,通过调节心肌细胞肌原纤维形成、促进糖原分解、诱导肥大相关基因转录、调节心脏传导系统发育及心肌细胞凋亡等,在心脏发育及心肌肥大的发生、发展过程起重要作用,本文对CRT在心肌肥大中的作用及其信号转导途径予以综述.     

脱落酸在植物体细胞胚胎发生中的调控作用

脱落酸是一种具有全面生理功能的植物激素,在植物体细胞胚胎发生发育过程中具有重要的作用。根据国内外最新的研究文献,从脱落酸对植物体细胞胚胎发生的影响、植物体细胞胚胎发生过程中内源脱落酸含量的变化、脱落酸对体细胞胚胎发生过程中基因表达、信号转导的调控和转基因的表达调控入手,概述了脱落酸在植物体细胞胚胎发生中的调控作用。     

外源性视黄酸对斑马鱼心血管系统发育的影响

目的观察不同浓度外源性视黄酸对斑马鱼早期胚胎和心血管系统发育的影响,为进一步研究视黄酸影响斑马鱼心脏前后轴(A-P轴)发育的分子机制提供形态学依据。方法选择斑马鱼胚胎孵育的3,6,9·5,12h四个时间点,用不同浓度视黄酸(1×10-6,1×10-7,4×10-8,1×10-8mol/L)处理斑马鱼胚胎,在解剖显微镜下实时观察斑马鱼胚胎心脏发育的全过程和视黄酸对斑马鱼心脏发育的影响。并采用胚胎整体原位杂交技术观察flk-1mRNA在斑马鱼胚胎的表达。结果1×10-6mol/L视黄酸可导致斑马鱼胚胎表现出多系统的严重畸形,胚胎很快死亡。在胚胎孵育的9·5、12h给与10-7~10-8mol/L浓度的视黄酸,胚胎只表现出心血管系统的畸形,其他系统无明显异常。胚胎整体原位杂交显示视黄酸对flk-1mRNA在斑马鱼胚胎血管的表达没有影响。结论视黄酸影响斑马鱼胚胎心脏发育有剂量依赖性和严格的时间窗,视黄酸影响心脏前后轴发育的关键时间是原肠胚晚期。视黄酸处理组胚胎的循环缺陷主要为心脏发育异常所致。10-7~10-8mol/L浓度视黄酸在9·5、12h处理斑马鱼胚胎可以作为研究心脏发育调控机制的动物模型。     

植物激素对体细胞胚胎发生的诱导与调节

以作者自己的工作为背景,结合国内外近几年的有关报道,综述了几种外源和内源激素对植物体细胞胚胎发生的诱导与调节作用。外源生长素和细胞分裂素是诱导离体培养细胞分化与增殖所必需的,2,4-D是诱导胚性愈伤组织的重要激素。在体细胞胚胎发生中内源激素含量和代谢的平衡起着关键的作用,而且外源和内源激素对诱导体细胞胚胎发生起相互调节作用。ABA在提高体细胞胚胎发生频率和质量上具有重要作用,同时,外源与内源ABA对体细胞胚胎发生起相互促进作用。本文还较为深入地讨论了这些激素诱导体细胞胚胎发生的可能作用机制。 Abstract:The paper summarizes the induced and regulatory effects of a few exogenous and endogenous hormones in plant somatic embryogenesis by our studies and related international reports.The exogenous auxin and cytokinin are necessary to induced differentiation and proliferation of cells of culture in vitro.2,4-D is an important hormone of induced embryogenic calluses.The contents and the metabolic balances of endogenous hormones have key effects for somatic embryogenesis.In addition,the exogenous and endogenous hormones have mutual regulatory effects for somatic embryogenesis.ABA has an important effect to improving the frequency and quality of somatic embryogenesis.Meanwhile,the exogenous and endogenous ABA have mutual promoted effects for somatic embryogenesis.The paper discusses possible mechanism of hormones-induced somatic embryogenesis in a deep-going way.     

植物小孢子胚胎发生机理

植物小孢子胚胎发生是作物遗传育种研究中的一个重要内容,也可以用来作为一个研究离体胚胎发育的优良模式系统.小孢子胚胎发生可以分为获得胚性潜能、启动细胞分裂和图式形成等3个特征阶段,对这3个阶段中主要的细胞分子特征进行综述.     

雌激素水平与围绝经期妇女心血管疾病相关性研究

目的：研究雌激素水平与围绝经期妇女心血管疾病的相关性。方法：回顾分析258例围绝经期患者的临床资料,研究心血管疾病发生情况。选取以合并心血管疾病患者为观察组,另选择无心血管疾病的患者为对照组,测定并比较两组患者的血清雌二醇（E2）水平。结果：258例患者中患有心血管疾病患者共50例（19.38％）,观察组和对照组患者年龄差异无统计学意义（P〉0．05）,血清E2含量分别为12．35±2．56pmol／L和46．84±3．85μmol／L,观察组显著低于对照纽（P〈0．05）。结论：心血管疾病的发生与雌激素水平下降直接相关。     

Atherosclerotic cardiovascular disease and dermatomyositis: an analysis of the Nationwide Inpatient Sample survey

Introduction

Increased rates of cardiovascular disease are implicated in several rheumatologic diseases. Our aim was to characterize dermatomyositis hospitalizations and evaluate cardiovascular-associated mortality in this patient population.

Methods

We examined the frequency and mortality rates of several atherosclerotic cardiovascular diagnoses and procedures among hospitalized adult patients with dermatomyositis using data from the US Nationwide Inpatient Sample (NIS) from 1993 to 2007. We compared the odds of death among hospitalized dermatomyositis patients with each cardiovascular diagnosis or procedure to those without, as well as to controls with cardiovascular diagnoses, using logistic regression.

Results

A total of 50,322 hospitalizations of dermatomyositis patients occurred between 1993 and 2007 (mean age 58 years, and 73% female). Of all dermatomyositis hospitalizations, 20% were associated with a concurrent atherosclerotic cardiovascular diagnosis or procedure. The overall in-hospital mortality was 5.7%. Dermatomyositis patients with any associated atherosclerotic cardiovascular diagnosis or procedure were twice as likely to die during the inpatient stay compared to dermatomyositis patients who did not have atherosclerotic cardiovascular disease (OR = 2.0 95% CI 1.7-2.5, p < 0.0001). The odds ratio for death in patients with both dermatomyositis and cardiovascular disease compared to controls with cardiovascular disease alone was 1.98 (95% CI 1.57-2.48) in multivariate adjusted models.

Conclusions

Approximately one fifth of dermatomyositis hospitalizations in the US were associated with an atherosclerotic cardiovascular diagnosis or procedure. These patients have double the risk of in-hospital death in comparison with controls and dermatomyositis patients without a cardiovascular diagnosis, making identification of these groups important for both prognostic purposes and clinical care.     

Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease

Background

People with type 2 diabetes mellitus are at high risk for cardiovascular disease. In some studies, the mortality rate among people with this condition has been equivalent to that among people with cardiovascular disease. We compared cardiovascular mortality between incident cases of diabetes and cardiovascular disease.

Methods

The study population was part of a random sample of 4376 men from Quebec, Canada, aged 35 to 64 years, who did not have cardiovascular disease in 1974 and who were followed until 1998. Three groups of incident cases were identified: diabetes without cardiovascular disease, first cardiovascular event (myocardial infarction, unstable angina or stroke) without diabetes, and both cardiovascular disease and diabetes. These cases were age-matched to a control group without diabetes or cardiovascular disease.

Results

During the 24-year follow-up period, new diabetes without cardiovascular disease was documented in 137 men. A first cardiovascular event without diabetes was documented in 527 men. Relative to the 627 controls, men with 1 of the 2 diseases of interest had higher cardiovascular mortality (age-adjusted relative risk [RR] 3.11, 95% confidence interval [CI] 1.96–4.92) for those with diabetes and 4.46 (95% CI 3.15–6.30) for those with cardiovascular disease). However, within the first 5 years after diagnosis, men with cardiovascular disease had higher cardiovascular mortality than men with diabetes (age-adjusted RR 2.03, 95% CI 1.01–4.08).

Interpretation

Men with isolated type 2 diabetes and men with isolated cardiovascular disease had similar cardiovascular mortality rates several years after initial diagnosis of either condition. These findings reinforce the need to prevent and optimally manage diabetes and cardiovascular disease.In 1971, type 2 diabetes mellitus was already considered an epidemic, affecting more than 170 million people worldwide.¹ In 2001, it was estimated that diabetes prevalence would increase by nearly 50% by the year 2010.¹ Epidemiologic studies performed in randomly sampled populations and initiated in the 1970s and 1980s have shown that diabetes increases the risk of all-cause death, as well as death due to cardiovascular disease and coronary artery disease.^2–23 In some studies,^12–17 but not all studies,^18–23 coronary or cardiovascular mortality among people with type 2 diabetes without previous cardiovascular disease was equivalent to that of people without diabetes who had had a first myocardial infarction or first cardiovascular event. Thus, there is controversy as to whether diabetes alone confers a risk of cardiovascular mortality similar to that associated with having had a first coronary or cardiovascular event. The differences in findings among various studies may be attributable to several factors such as age, sex, duration of diabetes and cardiovascular disease, ethnicity, cardiovascular risk factors and therapies. Furthermore, most studies used prevalent cases without considering the duration of cardiovascular disease or diabetes and did not exclude high-risk patients who had angina or intermittent claudication before the diagnoses of diabetes and cardiovascular disease.The rationale for undertaking the present study was the need for more information about the cardiovascular prognosis of men with type 2 diabetes relative to men with cardiovascular disease. We used incident instead of prevalent cases, without prior angina and without intermittent claudication. We speculated that the adverse prognosis associated with a diagnosis of diabetes would be similar to the prognosis associated with a diagnosis of cardiovascular disease over the long term but would be less similar over the short term. We formulated 2 hypotheses: first, that within the first few years after diagnosis, the risk of a fatal cardiovascular event would be higher among men with a first cardiovascular event and no diabetes than among men with type 2 diabetes and no cardiovascular disease; and second, that over the longer term, the risk of death within these 2 clinical subsets would tend toward equivalence.     

UACR在老年人群中的分布及其与心血管病危险因素的相关性研究

目的-观察老年人群尿微量白蛋白与尿肌酐比值（UACR）的分布情况,探讨其与心血管病危险因素的相关性。方法：选取2011年5月至2012年11月在我院接受体检的年龄在60岁以上的老年人922名,收集整理上述人群的基本临床资料。通过检测其清晨尿样,分析UACR在老年人群中的分布情况及和其于心血管病危险因素的关系。结果：①问卷调查结果：在接受调查的所有老年人中,有68名为健康人群,有724名为具有不同程度的心血管病危险因素人群。78．52％的老年人存在至少1个或多个心血管病危险因素。在众多心血管病危险因素中,患病率排在前三位的是：血脂异常、高血压和糖尿病。（2）UACR检测结果：健康人群中,男性UACR显著低于女性,差异有统计学意义（P〈0．05）;患有高血压,糖尿病和血脂异常人群的UACR显著高于健康人群,差异有统计学意义（P〈0．05）。结论：尿微量白蛋白与尿肌酐比值（UACR）与老年人群心血管疾病危险因素有着密切的联系,通过检测患者的UACR,为心血管疾病的治疗及预后奠定基础。     

心血管变异性的中枢调节数学模型

通过建立心血管变异性的数学模型,讨论心血管中枢对心血管调节的作用,血液血动力学公式、心交感和心迷走对心率的控制,压力感受器反射以及心血管中枢的活动性构成闭环的拍－拍心血管变异性数学模型。获得如下结果;模型仿真了,1）心血管变异性的三个主要的频率成分;2）传出神经活动也具有与心血管变异性相同的频谱特性;3）压力反射的S形曲线及其受心血管中枢的影响;4）心血管变异的昼夜节律现象。本模型成功地仿真了心血管变异性的主要特征,尤其提示了心血管中枢的活动对心血管变异性和压力反射敏感性有极大的影响。     

Fish consumption measured during pregnancy and risk of cardiovascular diseases later in life: an observational prospective study

Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12-17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease.     

Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats

Because apelin may play an important regulatory role in human cardiac dysfunction, we investigated alterations in cardiovascular content of apelin and its receptor, APJ, during hypertension and the effect of exercise training on the cardiovascular apelin/APJ system in hypertensive animals. Spontaneously hypertensive rats (SHRs) underwent swimming training consisting of 54 swimming sessions of 60 min each (6 days/week for 9 weeks). Systolic blood pressure (SBP) was verified weekly by tail-cuff plethysmography. Apelin levels in plasma and cardiovascular tissues were determined by radioimmunoassay. The level of apelin/APJ mRNA was determined by RT-PCR. SHRs showed severe hypertension and pathological cardiomegaly. The level of apelin immunoreactivity (apelin-ir) in plasma and ventricular and aortic tissues was lower, by 40%, 40% and 42% (all P<0.01), respectively, in SHRs than in control Wistar-Kyoto rats, and the mRNA level of apelin and APJ in myocardium and aorta was markedly decreased. Compared with sedentary SHRs, swimming-trained SHRs showed decreased SBP and elevated mRNA expression of apelin and APJ in cardiovascular tissues and elevated apelin-ir level in plasma, myocardium and aorta (all P<0.01). SBP and level of apelin-ir in plasma and cardiovascular tissues were negatively correlated. Long-term swimming training relieved the pathogenesis of hypertension and reversed the downregulation of the cardiovascular apelin/APJ system induced by hypertension, which suggests that the improving effect of exercise training on hypertension could be mediated by upregulating the cardiovascular apelin/APJ system.     

Young@Heart: empowering the next generation of cardiovascular researchers

In recognition of the increasing health burden of cardiovascular disease, the Dutch CardioVascular Alliance (DCVA) was founded with the ambition to lower the cardiovascular disease burden by 25% in 2030. To achieve this, the DCVA is a platform for all stakeholders in the cardiovascular field to align policies, agendas and research. An important goal of the DCVA is to guide and encourage young researchers at an early stage of their careers in order to help them overcome challenges and reach their full potential. Young@Heart is part of the DCVA that supports the young cardiovascular research community. This article illustrates the challenges and opportunities encountered by young cardiovascular researchers in the Netherlands and highlights Young@Heart’s vision to benefit from these opportunities and optimise collaborations to contribute to lowering the cardiovascular disease burden together as soon as possible.

     

糖皮质激素在孤束核内去甲肾上腺素／神经肽Y引起的心血管效应的影响及其机

本研究观察了糖皮质激素自身在孤束核ＮＴＳ内的心血管效应,以及它在ＮＴＳ内对ＮＡ／ＮＰＹ诱导的心血管活动变化的影响及机制。结果发现,大剂量地塞米松在大鼠ＮＴＳ的内能很快导致血压下降,血清中ＮＯ浓度升高。小剂量Ｄｅｘ在ＮＴＳ内能很快抑制ＮＡ／ＮＰＹ在ＮＴＳ内诱导的心血管效应,并维持较长时间。表明Ｄｅｘ对ＮＡ／ＮＰＹ在ＮＴＳ诱导的心血管效应,并维持较长时间。表明Ｄｅｘ对ＮＡ／ＮＰＹ在ＮＴＳ诱导的心血管效     

Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased?

OBJECTIVE--To quantify the effect of selection of relatively healthy women in studies reporting reduced relative risk for cardiovascular disease in postmenopausal women taking hormone replacement therapy. DESIGN--Review of the follow up studies reported in three recent meta-analyses to determine the effect of oestrogen therapy on both total cancer and cardiovascular disease. The same standard statistical methods as in the original analyses were used. MAIN OUTCOME MEASURES--Relative risks of total cancer and cardiovascular disease. RESULTS--In most of the follow up studies the relative risk for total cancer was below 1. The studies that showed the largest reduction in cardiovascular disease also showed the largest reduction in cancer, indicating a healthy cohort effect. Although heterogeneity within the studies prevented pooling, the best estimate for the protective effect on total cancer was a relative risk of 0.83 among women taking oestrogen (95% confidence interval 0.71 to 0.96), while in the same studies the relative risk for cardiovascular disease was 0.57 (0.50 to 0.64). CONCLUSIONS--Unintended selection of relatively healthy women for oestrogen therapy may have influenced the reported beneficial effect of oestrogen therapy on cardiovascular disease. It is unclear how much of the cardioprotection is due to this selection. Universal preventive hormonal replacement therapy for postmenopausal women is unwarranted at present.