冠心病患者apoE基因调控序列-219(G/T)多态性及与血脂的关系

为了研究载脂蛋白E(apoE）基因调控序列－219（G／T）多态性与人类冠心病（CHD）及其血脂水平的关系，本文采用聚合酶链反应结合了限制性片段长度多态性方法。分析了108例健康人及86例冠心病患者的－219（G／T）基因型。PCR产物直接测序验下。我们发现冠心病组apoE－219（T／T）基因型频率（0．651）和T等位基因频率（0．767）分别显著高于对照组（0．444，0．653，P＜0．05）；冠心病组和对照组T／T基因型者血清总胆固醇高于G／G基因型者。这一结果提示apoE调控区基因多态性可能影响冠心病的发生。推测apoE－219（T／T）基因型是冠心病的危险因子之一。     

GP78基因多态性与冠心病相关

目的探讨GP78基因多态性与冠心病的相关性。方法 Taq Man SNP基因分型法对1109例(557例冠心病患者+552例对照者)无血缘关系的研究对象进行基因分型,并应用病例对照的研究方法进行相关性分析。结果GP78基因rs2617849位点的基因分型和等位基因频率在冠心病组和对照组之间的分布存在明显差异(P0.05),冠心病组携带TT基因型(TT vs CC+CT)和T等位基因高于对照组(P0.05),在排除吸烟、高血压、糖尿病和低密度脂蛋白胆固醇等混杂因素后,仍存在显著性差异(95%CI:1.035~1.736,P0.05)。结论 GP78基因的rs2617849位点多态性与冠心病相关,rs2617849的TT基因型和T等位基因可作为冠心病易感基因标记。     

Risk-factor changes in wives with husbands at high risk of coronary heart disease (CHD): The spin-off effect

This study of 220 wives of participants from four of the 22 clinics in the Multiple Risk Factor Intervention Trial (MRFIT) addresses the question of whether spouses of men exposed to a continuous coronary heart disease (CHD) risk-factor intervention program (SI group) make changes in their own risk status compared to wives of men who did not receive the intervention program (UC group). Total serum cholesterol and low-density lipopro-tein (LDL) cholesterol were significantly lower for the SI wives. These differences were found for both hypertensive and normotensive wives, although the magnitudes were much greater for the hypertensive wives. There were also significant differences between the two groups of wives in the food-record rating and in dietary-knowledge scores, indicating that the probable mechanism for the beneficial effect of the intervention with respect to cholesterol levels was the change in the family diet. Although not statistically significant, differences indicating a lower risk for SI wives were found for diastolic blood pressure. There was also a greater mean reduction in cigarettes per day for SI wives who smoked.This work was supported by NHLBI Grant l RO1 HL 27142-01.     

Animal models of coronary heart disease

Cardiovascular disease, predominantly coronary heart disease and stroke, leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions. The dominant pathologic foundation for cardiovascular disease is atherosclerosis and, as to coronary heart disease, coronary atherosclerosis and resulting lumen stenosis, even total occlusions. In translational research, several animals, such as mice, rabbits and pigs, have been used as disease models of human atherosclerosis and related cardiovascular disorders. However, coronary lesions are either naturally rare or hard to be fast induced in these models, hence, coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions, thus unrepresentative of human coronary heart disease progression and pathology. In this review, we describe the progress of animal models of coronary heart disease following either spontaneous or diet accelerated coronary lesions.     

不同剂量瑞舒伐他汀对冠心病患者Rho激酶活性和内皮功能影响的比较

目的：研究不同剂量瑞舒伐他汀对冠心病患者Rho激酶活性和内皮功能影响。方法：选取2014年6月至2015年11月我院接收的稳定型心绞痛患者128例,按照随机数字表法将其分为对照组、实验A、实验B、实验C四组,每组各32例。对照组参照临床用药指南,根据患者病情给予硝酸酯类、抗血小板凝集、抗凝、降血糖、控制血压等常规治疗,实验A、B、C三组患者在常规治疗的基础上分别予以口服5、10、20 mg不同剂量的瑞舒伐他汀,频率均为每天1次,持续时间为8周。检测并比较4组患者治疗前后的超敏C反应蛋白(hs-CRP)、Rho激酶(Rho kinase,ROCK)活性、肱动脉内皮依赖性舒张功能(lfow-mediated dilatation,FMD)、总胆固醇(TC)的差异以及各组患者出现的不良反应情况。结果：治疗前,对照组以及实验A、B、C组患者的指标检测无明显差异,无统计学意义(P>0.05)。治疗后,对照组的hs-CRP含量为(3.13±0.67) mg/L,实验A、B、C组分别为(2.67±0.73)、(2.15±0.44)、(1.87±0.32) mg/L,均与对照组差异明显(P<0.05),且hs-CRP含量随瑞舒伐他汀剂量增大而降低;对照组Rho激酶(ROCK)活性为(62.73±12.67)%,实验A、B、C组分别为(53.71±10.98)%、(41.63±9.61)%、(35.46±9.24)%,均明显低于对照组(P<0.05),且随瑞舒伐他汀剂量增大,ROCK活性越来越弱;对照组FMD水平为(4.27±1.63)%,实验A、B、C组分别为(6.62±1.51)%、(8.15±1.32)%、(9.97±1.38)%,均明显高于对照组(P<0.05),且瑞舒伐他汀剂量越大,FMD水平越高;对照组TC含量为(5.76±0.73) mmol/L,实验A、B、C组分别为(5.01±0.73)、(4.92±0.62)、(4.21±0.58) mmol/L,均明显低于对照组(P<0.05),且随瑞舒伐他汀剂量增大,TC含量越来越低;不良反应情况：实验A组患者血清转氨酶超标、横纹肌溶解以及肌肉酸痛出现次数分别为1、2、1例,B组为1、3、2例,C组为2、2、1例,结果对比无统计学差异(P>0.05)。结论：对于冠心病患者而言,瑞舒伐他汀能够抑制Rho激酶活性,缓解患者内皮功能紊乱状况,明显改善血管内皮功能,并存在量效关系,且使用高剂量的瑞舒伐他汀是安全的。     

冠心病患者心率变异性分析

目的研究冠心病患者心率变异（HRV）的变化规律及临床意义。方法选择50例无心律失常冠心病患者（冠心病组）、30例伴心律失常冠心病患者（心率失常组）与52例正常成人自愿者（正常组）进行24h动态心电图HRV指标比较研究。结果与正常组比较,冠心病患者SDNN、SDANN、RMSSD、PNN50和HF指标均降低,LF指标升高,具有显著差异。伴心律失常与无心律失常冠心病患者比较,HRV指标异常变化趋于恶化。结论冠心病患者心脏自主神经调节功能受到损害,迷走神经活性减弱,交感神经活动占优势。     

Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease

Objective: Fibroblast growth factor-21 (FGF-21) has been discovered as a strong hormone, plays an important role in lipid metabolism, glucose metabolism, associated with several diseases such as obesity, metabolic syndrome, diabetes mellitus, and cardiovascular events; however, no evidence is available concerning the relationship of FGF-21 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). Methods: Twenty-four rheumatic heart disease patients were divided into two groups, 12 cases with AF and 12 cases with sinus rhythm (SR). Clinical characteristics and blood samples were collected before surgery; right atrial appendage samples were taken in the surgery of valve replacement. HE staining was performed to determine cross-sectional area of atrial myocytes; Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to evaluate the degree of cardiac fibrosis; the level of FGF-21 was evaluated via enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and real-time polymerase chain reaction (PCR). Results: Compared with SR group, cross-sectional area of atrial myocytes and collagen volume fraction were significantly increased in the atrial tissue of AF group. The distribution of FGF-21 in the AF group was remarkably higher than SR group. In addition, plasma and mRNA levels of FGF-21 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. Using linear correlation analysis, the expression level of FGF-21 was found to be positively related to the degree of atrial fibrosis. Conclusion: FGF-21 might involve in the development and maintenance of atrial fibrosis in atrial fibrillation with rheumatic heart disease, and FGF-21 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.     

真武汤加味对冠心病心力衰竭患者左心功能的影响

目的：评价真武汤加味对冠心病心力衰竭患者左心功能的影响。方法：100例冠心病心力衰竭患者随机分为治疗组和对照组,各50例。对照组用西医常规药物治疗,治疗组用西医常规药物加真武汤加味治疗,于入院当天和入院第90天行二维超声心动图测量,计算左心室舒张末内径、左心室收缩末内径和左室射血分数,并抽血检查血浆N端脑钠肽前体水平的变化。结果：与治疗前比较,两组的左心室舒张和收缩末内径均显著缩小（均P〈0．01）,左心室射血分数均明显增加（均P〈0．01）,血浆N端脑钠肽前体水平均显著降低（均P〈0．01）,用药后治疗组各指标改善明显优于对照组（均P〈0．011。结论：西医常规药物加真武汤加味治疗可以显著改善冠心病心力衰竭患者的左心功能和心室重构。     

冠心病冠状动脉搭桥术前后心电图变化的研究

目的探讨冠心病人冠状动脉搭桥术(CABG)前后心电图的变化。方法通过25例冠心病CAGB患者术前与术后7天、14天、21天及30天阶段比较心电图的动态变化。结果与术前(4.5±2.3天)比较,ST段压低>1.0mm。T波低平、双向和倒置第一周显著增多,此后ST段压低者减少到术前水平,T波低平、双向和倒置非常显著地减少。结论冠心病患者CABG后出现一过性ST段压低变化,T波低平、双向和倒置,此后上述改变逐渐减少至恢复到术前水平。     

Ageing is associated with reduced basal and stimulated release of nitric oxide by the coronary endothelium

The ageing process is known to be associated with biochemical and functional changes in the heart. In an attempt to determine whether the ability of the coronary endothelium to secrete nitric oxide (NO) both at rest and in response to pharmacological stimulation is age dependent, we studied four groups of rats of different ages (1, 5, 15 and 26 months, respectively). Basal release of NO by endothelium as assessed by response of coronary flow to l -monomethylarginine, an inhibitor of NO synthase, was higher in the younger age groups. Similarly, the response of coronary flow to 5-hydroxytryptamine, a selective probe of endothelial capacity to secrete NO, was diminished in the older animals. This was confirmed by direct measurement of NO by chemiluminescence in the coronary effluent. In contrast, the response to glyceryl trinitrate appeared to be unaltered by age. It is concluded that in rats, basal and stimulated release of nitric oxide by the coronary endothelium deteriorates with age.     

Effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model

Objective: Our objective is to explore the effect of curcumin on permeability of coronary artery and expression of related proteins in rat coronary atherosclerosis heart disease model. Methods: 45 healthy male Wistar rats of clean grade were selected and divided into treatment group, model control group and blank control group. The rats in the treatment group and model control group received high-fat diet for 12 weeks and intraperitoneal injection of VD₃ to establish rat coronary atherosclerosis heart disease model. After modeling, the rats in the treatment group received gavage of 100 mg/(kg·d) curcimin, and the rats in the model control group and blank control group received gavage of 5 ml/(kg·d) distilled water, the intervention time was 4 weeks. After intervention, the rats were killed, and the hearts were dissected to obtain the samples of coronary artery. After embedding and frozen section, immunofluorescence method was used to detect the change of endarterium permeability in 3 groups, Western blot was used to detect matrix metalloproteinase-9 (MMP-9) and CD40L in coronary artery tissue, and enzyme linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α) and C reaction protein (CRP). Results: After modeling, compared with the blank control group, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterin (LDL-c) in the treatment group and model control group were significantly higher (P<0.05), however, high density lipoprotein cholesterin (HDL-c) was significantly lower. The pathological sections showed that there was lipidosis in rat coronary artery in treatment group and model control group, indicating that the modeling was successful. Immunofluorescence showed that there was only a little fluorochrome permeability in artery in blank control group, there was some fluorochrome permeability in artery in the treatment group and there was a lot of fluorochrome permeability in artery in the model control group. MMP-9 and CD40L in coronary artery tissue in the model control group were significantly higher than the treatment group (P<0.05), MMP-9 and CD40L in coronary artery tissue in the treatment group were significantly higher than the blank control group (P<0.05); serum TNF-α and CRP in the model control group were significantly higher than the treatment group (P<0.05), which were significantly higher in the treatment group than the blank control group (P<0.05). Conclusion: Rat coronary atherosclerosis heart disease model can be successfully established by feeding with high-fat diet and intraperitoneal injection of VD₃, the permeability of coronary artery in coronary heart disease rat model is significantly increased, which may be related to up-regulation of MMP-9, CD40L, TNF-α and CRP expression. Application of curcumin can inhibit expression of MMP-9, CD40L, TNF-α and CRP to improve the permeability of coronary artery.     

Support and coronary heart disease: the importance of significant other responses

In addition to the recognized benefits of social support, there is evidence across several health-related disorders suggesting that specific types of support can contribute to negative outcomes. Informed by theory and research examining the role of pain-related interpersonal interactions in the perpetuation of chronic pain, this study examined whether specific responses from significant others to expressions of coronary heart disease(CHD) related symptoms and incapacity are associated with level of symptoms, degree of disability, and depressive symptom severity among persons with symptomatic CHD. Forty-nine persons with CHD completed self-report questionnaires of the constructs of interest. Regression analyses revealed that degree of perceived solicitous responding to CHD symptoms was associated with increased symptom severity, disability, and depressive symptoms. Results are consistent with an operant-conditioning model and suggest that positive attention from significant others contingent on expressions of CHD symptoms may unwittingly serve to reinforce symptom occurrence and expression, concomitant disability, and emotional distress.     

Use of lipid-modulating drugs in complicated course of coronary heart disease

We present the results of the study of lipid-modulating drugs (pravastatin, atorvastatin, simvastatin, and fibrate gemfibrozil) in complicated coronary heart disease (acute coronary syndrome without ST elevation, chronic heart failure. In acute coronary syndrome statins produced a positive effect on some studied parameters, while in heart failure only the safety of short-term therapy with statins was demonstrated. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Supplement 2, pp. 67–75, April, 2007     

L-选择素基因多态性与冠状动脉粥样硬化性心脏病易感性的相关性研究

目的探讨L-选择素基因P213S多态性是否与冠状动脉粥样硬化性心脏病有关联。方法采用病例-对照研究，对212例经冠状动脉造影确诊的冠心病患者和230名正常对照者进行研究。应用聚合酶链反应限制性片段长度多态性（polymemse chain reaction-restriction fragment length polymorphism，PCRRFLP）技术测定L-选择素基因多态性。结果冠心病组213P等位基因频率明显高于对照组（77．59％vs69．35％，P=0．006）。PP纯合子患冠心病的风险是SS纯合子的2．70倍（95％CI：1．07～6．81），且经Logistic回归分析校正性别、年龄、体重指数、血清总胆固醇、甘油三酯、高密度脂蛋白-胆固醇和低密度脂蛋白-胆固醇等相关因素之后，差异仍具有统计学意义。根据冠状动脉造影结果进一步对冠心病患者进行分组后分析，发现L-广选择素基因P213S多态性与病变血管支数及疾病程度无相关性。结论L-广选择素213P等位基因可能与我国汉族人冠心病的易感性相关联。     

结合珠蛋白基因1/2多态性与中国人冠心病易感性的关联研究

目的 通过分析冠心病患者及冠脉正常组中结合珠蛋白(haptoglobin,HP)基因1/2多态性分布,初步探讨HP基因1/2多态性与冠心病易感性的关系.方法 经冠脉造影确诊冠心病组189例,冠脉正常对照组242名;采用聚合酶链反应-限制性片段长度多态性技术检测所有受试者HP基因型.结果 冠心病组HP基因型分布与对照组相比差异有统计学意义(P=0.002),表现为HP2-2基因型在冠心病组的频率明显高于对照组(0.54vs.0.35,P=0.000),单因素分析显著增加冠心病的风险(OR=2.166,95%CI:1.467～3.196),HP2等位基因的频率也明显高于对照组(0.74 vs.0.61).同时,多因素Logistic回归分析表明HP2-2基因型是冠心病的独立危险因素(P=0.002;OR=2.101,95%CI:1.311～3.367).结论 HP2-2基因型与冠心病的发生相关,可能是冠心病发病的独立危险因子;HP2等位基因可能是中国人冠心病的易感基因.

Abstract：

Objective To assess the association of haptoglobin (HP)1/2 polymorphism with coronary heart disease (CHD) in Chinese Hans. Methods One hundred and eighty-nine CHD patients and 242 healthy controls confirmed with angiography were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to genotype the HP1 and HP2 alleles and genotype frequencies in cases and controls were compared. Results The frequency of HP2-2 genotype was significantly higher in CHDs than in controls (0. 54 vs. 0.35, P=0.000). The HP2-2 genotype significantly increased the risk for CHD in univariable analysis (OR= 2. 165, 95% CI: 1. 467-3. 196). Multifactor Logistic regression analysis indicated that HP2-2 genotype is an independent risk factor to CHD (P=0.002;OR=2. 101, 95% CI: 1. 311-3. 367). Similarly, the HP2 allele frequency in the CHD group was significantly higher than that in the control subjects (0.74 vs. 0. 61, P= 0. 000). Conclusion The HP2-2genotype is associated with CHD in Chinese. HP2-2 genotype may be an independent risk factor to CHD,and HP2 allele may be a genetic susceptibility factor to CHD in Chinese.     

The C-480T hepatic lipase polymorphism is associated with HDL-C but not with risk of coronary heart disease

High-density lipoprotein cholesterol (HDL-C) is a known predictor of coronary heart disease (CHD). Studies have shown that the C-480T polymorphism of the hepatic lipase (HL) gene is predictive of HDL-C; however, its observed relationship with the risk of CHD has been inconsistent. We analysed four biallelic polymorphisms in the HL gene in participants from three independent Western Australian populations. Samples were collected from two cross-sectional studies of 1111 and 4822 community-based subjects assessed for cardiovascular risk factors, and a third sample of 556 subjects with physician-diagnosed CHD. Genotypes were tested for association with plasma lipids and the risk of CHD. All polymorphisms were highly correlated (D' > 0.97, r(2) > 0.90); therefore, only C-480T was analysed. The -480T allele was significantly associated with an increase in HDL-C of between 0.08 and 0.16 mmol/l in all three populations (p < 0.001). No associations with other lipids were observed, nor was an association with CHD in a case-control study of males. The TT genotype was however associated with decreased risk of myocardial infarction among cases (odds ratio = 0.39, 95% confidence interval = 0.19-0.78, p = 0.008). These findings replicate those of previous studies in three independent populations and suggest that the genetic determinants of CHD are complex and cannot be entirely explained through intermediate phenotypes.     

红花注射液治疗冠心病心绞痛疗效观察

目的:观察红花注射液治疗冠心病心绞痛的临床疗效。方法:选择100例冠心病心绞痛的病例,随机分红花组及对照的丹参两个治疗组,疗程两周,详细记录治疗前后的临床表现,心电图,血糖,血流变检查的变化。结果:红花,丹参均可明显改善冠心病心绞痛的临床症状和心电图改变,以红花较显著。红花还有降血糖,血脂作用,显著改善血流变指标。结论:红花注射液是治疗冠心病心绞痛的理想药物。     

Cerebral capillary endothelial cells are covered by the VEGF-expressing foot processes of astrocytes

Molecules that have crucial functions in both nervous and vascular systems have attracted keen attention recently, and the name "angioneurins" has been proposed. The most striking example of angioneurins is vascular endothelial growth factor A (VEGF), which was originally identified as a key regulator of angiogenesis and has only recently been found to have important functions in the nervous system. In this study, we compared VEGF expression in the vasculature in the brain with that in the aorta and the vasculature in the kidney in mice. In larger vessels containing smooth muscle cells, VEGF was expressed by smooth muscle cells covering the lining of endothelial cells, both in and outside the brain. In cerebral capillaries lacking smooth muscle cells, endothelial cells were closely covered by VEGF-expressing foot processes of astrocytes, whereas capillaries were surrounded by VEGF-expressing processes of podocytes in the renal glomeruli. We also found that cultured cerebral microvessel endothelial cells do not express VEGF, whereas cultured cortical astrocytes do express VEGF.     

急性冠状动脉综合征介入治疗前后脑钠肽变化及对临床预后的判断

目的通过测定急性冠状动脉综合征患者介入治疗前后血浆脑钠肽（BNP）水平的变化,探讨急性冠状动脉综合征介入治疗（PCI）对急性冠状动脉综合征患者血浆BNP变化及对临床病情和预后的判断。方法冠心病介入治疗（PCI）168例,分为存活组（143例）和死亡组（25例）;对存活组患者随访至6个月分别测定血浆BNP及死亡、再入院率,超声心动图检查（UCG）左室射血分数（LVEF）。结果PCI术后血浆BNP水平比术前明显降低,从术前的血BNP浓度在（176±27）ng／L逐渐升高,至术后6个月降低到（98±6）ng／L,与术前相比差异具有统计学意义（P〈0．05）。死亡组患者术前血BNP浓度水平比存活组明显升高（P〈0．05）。存活组和死亡组LVEF[（57．0±14．1）％比（31．0±15．0）％,P〈0．01]有统计学意义,Logistic多变量逐步回归分析显示,BNP是预测ACS患者PCI治疗预后的独立预测因子,且与LVEF呈负相关。结论PCI可降低ACS患者血液BNP水平,但术前BNP水平,常提示预后不良     

炎症反应在冠心病患者中的作用及临床意义

目的 :探讨炎症反应与冠心病 (CHD)之间的关系。方法 :10 1例CHD患者分为 3组 ,即稳定型心绞痛 (SAP)组 (19例 )、不稳定型心绞痛 (UAP)组 (33例 )和急性心肌梗死 (AMI)组 (49例 )。分别采用免疫浊度法及血细胞计数仪 ,检测外周血中的C 反应性蛋白 (CRP)水平及白细胞 (WBC)总数。 2 0例AMI死亡患者的心肌组织切片进行病理学检查。结果 :AMI和UAP组血中CRP的水平和WBC总数明显高于对照组 (P <0 .0 1)。病理学检查发现 ,AMI患者心肌中有大量白细胞浸润。结论 :CHD发生、发展有炎症反应的参与 ,检测血中的CRP和WBC可作为监测病情、预测冠心病危险性的常规指标之一