Studies on the Induced Synthesis of Maleate cis-trans Isomerase by Malonate

Maleate cis-trans isomerase in Alcaligenes faecalis IB–14 was induced by malonate and purified about 100-fold over the crude cell-free extract by treatments of ammonium sulfate fractionation, Sephadex G–100 gel filtration, DEAE-cellulose and DEAE-Sephadex A–50 column chromatography. The preparation was shown to be monodisperse on ultracentrifugal analysis and Svedberg value was found to be 3.84 S.

The enzyme was most active at pH value around 8.3 and was stable over the range of pH 5.0 to 7.0 in the presence of dithiothreitol (DTT) for a few weeks, but in the absence of it, the enzyme activity was markedly decreased, especially in the alkaline region. The enzyme activity was inhibited by various sulfhydryl reagents and oxidizing agents, whereas it was not affected by metal chelating agents. The inhibition by Hg²⁺ and PCMB was overcome by the addition of sulfhydryl compounds such as DTT, 2-mercaptoethanol, l-cysteine and glutathione. It was observed that the enzyme did not require co-factor for its function.

Kinetic studies showed that Michaelis constant for maleate was 2.8×10^?3 m and the enzyme did not catalyze the reverse reaction.     

阿托伐他汀对急性心肌梗塞患者hs-CRP及血脂水平的影响

目的:研究阿托伐他汀对急性心肌梗塞患者超敏C反应蛋白(hs-CRP)及血脂水平的影响。方法:选取2012年1月到2015年1月我院收治的急性心肌梗塞患者80例,按照随机数字表法将患者分为研究组和对照组,每组40例,对照组给予常规治疗,研究组在对照组的基础上给予阿托伐他汀治疗,比较治疗前后两组hs-CRP和总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。结果:两组治疗后hs-CRP较治疗前显著降低(P0.05),且研究组治疗后hs-CRP显著低于对照组,(P0.05);治疗后两组TC、TG和LDL-C显著低于治疗前,HDL-C显著高于治疗前(P0.05),且治疗后研究组TC、TG和LDL-C显著低于对照组,HDL-C显著高于对照组(P0.05)。结论:阿托伐他汀治疗急性心肌梗塞具有较好的效果,能有效降低hs-CRP水平,改善患者血脂水平。     

不同性别急性心梗患者的临床特征及院内治疗预后分析

目的:观察首次确诊为急性心肌梗死(AMI)患者的临床特征并分析不同性别人群的在入院治疗及院内短期预后的差异。方法:回顾性分析2010年2月至2012年4月在沈阳军区总医院心内科初次确诊为AMI的患者271例,并按性别分为两组,其中男性组180例,女性组91例,统计其临床特征、入院后的药物和手术治疗情况,以及院内并发症及预后情况,分析总结两组患者各自的特点和差异。结果:女性患者的年龄要大于男性患者(63±14vs71±11,P0.001),且同时更易患有高血压等心血管疾病合并症(73.3%vs 58.2%,P0.05)。女性患者的发病至入院治疗时间长于男性(P0.001),且入院后行PCI治疗的比例要明显低于男性患者(67%vs 79.4%,P0.05)。初步分析结果表明,女性患者的院内死亡率高于男性(11%vs 3.3%,OR:3.11,95%CI:1.53-7.15),但排除不均衡因素的影响后,男女患者的院内死亡率无明显差异(OR:2.11,95%CI:0.68-5.12)。结论:两性AMI患者的临床特征、入院后治疗及院内短期预后均存在一定差异。根据女性患者的临床特征和院内治疗及预后的现状,应进一步加强对女性高危人群的冠心病诊治知识普及和教育,且对入院后的女性患者应采取更为积极的药物和介入手术治疗手段,以改善预后。     

动脉粥样硬化大鼠心肌梗死时钙敏感受体表达的变化及其作用机制

目的:探讨动脉粥样硬化大鼠心肌梗死时钙敏感受体表达的变化及其作用机制。方法:Wistar大鼠随机分为4组:正常对照组(Control);异丙肾上腺组(ISO);动脉硬化组(AS);动脉硬化+异丙肾上腺素组(AS/ISO)。采用腹腔注射VD3和高脂饮食及大剂量异丙肾上腺素(ISO 200 mg/kg)皮下注射复制大鼠在体动脉粥样硬化心肌梗死模型,应用RT-PCR测定心肌组织中Ca SR、Bax、Bcl-2和caspase-3 m RNA的表达变化;TUNEL染色观察心肌细胞凋亡情况;光镜观察心肌形态学变化;紫外分光法检测血清肌酸激酶(CK)、电化学免疫发光法检测肌钙蛋白T(c Tn T)水平。结果:与正常组比较,ISO组CK活性、c Tn T水平以及Ca SR、Bax和caspase-3的表达均增加,同时Bcl-2表达减少,心肌细胞损伤严重,AS/ISO的心肌损伤进一步加重。结论:Ca SR的表达增多参与了动脉硬化大鼠心肌梗死的发生,其机制可能与促进心肌细胞凋亡有关。     

血栓通注射液联合阿托伐他汀对急性脑梗死患者血脂和血液流变学的影响

目的:研究阿托伐他汀片与血栓通注射液联合治疗对脑梗死患者血脂及血液流变学的影响。方法:选取我院从2012年2月到2014年2月收治的急性脑梗死患者100例,分成两组,每组各50例。对照组静脉滴注血栓通注射液,试验组静脉滴注血栓通注射液加口服阿托伐他汀片治疗。14天后观察两个组的治疗效果,并且进行血脂(TC、TG、LDL-C、HDL-C)、血液流变学(血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数)等指标的检测,以及疗效及不良反应情况。结果:治疗后试验组TC、TG、LDL-C低于对照组,HDL-C高于对照组,且具有统计学意义(P0.05)。治疗后,试验组血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数均低于对照组,且具有统计学意义(P0.05)。试验组总有效率为88.0%(44/50),高于对照组的66.0%(33/50)(P0.05)。试验组发生不良反应发生率与对照组比较无统计学意义(P0.05)。结论:阿托伐他汀片联合血栓通注射液对于脑梗死患者的血脂和血液流变学的影响疗效显著,且具有明显的降脂效果。     

急性非ST 段抬高性心肌梗死患者血清尿酸水平与N末端B 型钠尿肽原的相关性分析

目的:探讨急性非ST段抬高性心肌梗死(NSTEMI)患者血清尿酸水平与N末端B型钠尿肽原(NT-pro BNP)的相关性分析。方法:将143例NSTEMI患者按照入院时血清尿酸四分位数分为四组:Ⅰ组(尿酸284.18μmol/L)、Ⅱ组(284.19~336.53μmol/L),Ⅲ组(336.54~390.78μmol/L),Ⅳ(尿酸390.79μmol/L);按照血清NT-pro BNP中位数分为2组:NT-pro BNP571.56 pg/m L组和NT-pro BNP≥571.56 pg/m L组;比较各组相关指标的差异。结果:Ⅰ组、Ⅱ组、Ⅲ组及Ⅳ组四组的NT-pro BNP、GRACE危险评分、CK-MB、LEVF、c Tn I比较统计学差异(P0.05),Ⅳ组NT-pro BNP、GRACE危险评分、c Tn I、CK-MB高于Ⅰ组、Ⅱ组、Ⅲ组,Ⅲ组高于Ⅰ组、Ⅱ组(P0.05);NT-pro BNP≥571.56 pg/m L组血清尿酸、GRACE危险评分、c Tn I、CK-MB高于NT-pro BNP571.56pg/m L组(P0.05)。血清尿酸分别与NT-pro BNP、GRACE危险评分呈现正相关(P0.05)。结论:血清尿酸水平与NSTEMI患者的NT-pro BNP密切相关,临床检测血清尿酸水平对于评估NSTEMI患者NT-pro BNP水平具有重要的意义。     

Acute stress is detrimental to heart regeneration in zebrafish

Psychological stress is one of the factors associated with human cardiovascular disease. Here, we demonstrate that acute perceived stress impairs the natural capacity of heart regeneration in zebrafish. Beside physical and chemical disturbances, intermittent crowding triggered an increase in cortisol secretion and blocked the replacement of fibrotic tissue with new myocardium. Pharmacological simulation of stress by pulse treatment with dexamethasone/adrenaline reproduced the regeneration failure, while inhibition of the stress response with anxiolytic drugs partially rescued the regenerative process. Impaired heart regeneration in stressed animals was associated with a reduced cardiomyocyte proliferation and with the downregulation of several genes, including igfbp1b, a modulator of IGF signalling. Notably, daily stress induced a decrease in Igf1r phosphorylation. As cardiomyocyte proliferation was decreased in response to IGF-1 receptor inhibition, we propose that the stress-induced cardiac regenerative failure is partially caused by the attenuation of IGF signalling. These findings indicate that the natural regenerative ability of the zebrafish heart is vulnerable to the systemic paracrine stress response.     

In Vivo Quantitative Assessment of Myocardial Structure,Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).     

Suppressive effect of epigallocatechin‐3‐O‐gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo

Epigallocatechin‐3‐O‐gallate (EGCG), derived from green tea, has been studied extensively because of its diverse physiological and pharmacological properties. This study evaluates the protective effect of EGCG on angiotensin II (Ang II)‐induced endoglin expression in vitro and in vivo. Cardiac fibroblasts (CFs) from the thoracic aorta of adult Wistar rats were cultured and induced with Ang II. Western blotting, Northern blotting, real‐time PCR and promoter activity assay were performed. Ang II increased endoglin expression significantly as compared with control cells. The specific extracellular signal‐regulated kinase inhibitor SP600125 (JNK inhibitor), EGCG (100 μM) and c‐Jun N‐terminal kinase (JNK) siRNA attenuated endoglin proteins following Ang II induction. In addition, pre‐treated Ang II‐induced endoglin with EGCG diminished the binding activity of AP‐1 by electrophoretic mobility shift assay. Moreover, the luciferase assay results revealed that EGCG suppressed the endoglin promoter activity in Ang II‐induced CFs by AP‐1 binding. Finally, EGCG and the JNK inhibitor (SP600125) were found to have attenuated endoglin expression significantly in Ang II‐induced CFs, as determined through confocal microscopy. Following in vivo acute myocardial infarction (AMI)‐related myocardial fibrosis study, as well as immunohistochemical and confocal analyses, after treatment with endoglin siRNA and EGCG (50 mg/kg), the area of myocardial fibrosis reduced by 53.4% and 64.5% and attenuated the left ventricular end‐diastolic and systolic dimensions, and friction shortening in hemodynamic monitor. In conclusion, epigallocatechin‐3‐O‐gallate (EGCG) attenuated the endoglin expression and myocardial fibrosis by anti‐inflammatory effect in vitro and in vivo, the novel suppressive effect was mediated through JNK/AP‐1 pathway.     

Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post‐myocardial infarction rats

Danqi soft capsule (DQ) is a traditional Chinese medicine containing Salvia miltiorrhiza and Panax notoginseng; it is safe and efficient in treating ischaemic heart diseases. The purpose of the present study was to assess whether DQ could prevent infarct border zone (IBZ) remodelling and decrease ventricular arrhythmias occurrence in post‐myocardial infarction (MI) stage. MI was induced by a ligation of the left anterior descending coronary artery. DQ was administered to the post‐MI rats started from 1 week after MI surgery for 4 weeks. The results showed that DQ treatment significantly attenuated tachyarrhythmia induction rates and arrhythmia score in post‐MI rats. In echocardiography, DQ improved left ventricular (LV) systolic and diastolic function. Histological assessment revealed that DQ significantly reduced fibrotic areas and myocyte areas, and increased connexin (Cx) 43 positive areas in IBZ. Western blot revealed that DQ treatment significantly reduced the protein expression levels of type I and III collagens, α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1) and Smad3 phosphorylation, while increasing Cx43 amounts. Overall, these findings mainly indicated that DQ intervention regulates interstitial fibrosis, Cx43 expression and myocyte hypertrophy by TGF‐β1/Smad3 pathway in IBZ, inhibits LV remodelling and reduces vulnerability to tachyarrhythmias after MI. This study presents a proof of concept for novel antiarrhythmic strategies in preventing IBZ remodelling, modifying the healed arrhythmogenic substrate and thus reducing susceptibility to ventricular arrhythmias in the late post‐MI period.