牛磺酸对培养乳鼠心肌细胞缺氧坏死的保护作用

目的　观察牛磺酸 (Tau)对缺氧引起的心肌细胞坏死有无直接保护作用。方法　将培养心肌细胞分为正常对照、Tau对照缺氧 Tau和缺氧 4个组。测定培养细胞上清液中肌酸磷酸激酶 (CPK)活性 ,用原子吸收法测定细胞内钙、镁含量 ,Annexin V- FITC/ PI双染流式细胞术和台盼蓝染色镜检检测坏死细胞。结果　 Tau可使缺氧时培养细胞上清液中CPK活性降低 30 % ,坏死细胞减少大约 2 0 %。减少细胞内钙超载和镁丢失。结论　 Tau对缺氧导致的心肌细胞坏死有直接保护作用 ,此作用可能与减少细胞内钙超载和镁丢失有关。     

丹参注射液加强缺血预处理对大鼠心肌的保护作用

以整体麻醉SD大鼠心脏冠状动脉左前降支结扎／松开作为缺血／再灌注动物模型，研究丹参注射液（SM）在加强缺血须处理（IP）的心肌保护中的作用。结果显示，IP能减轻复灌性心律失常的严重程度，缩小心肌梗死范围；SM能缩小心肌梗死范围；SM联合IP与单纯IP比较，心肌梗死范围进一步缩小；SM联合IP与单纯SM比较，心律失常严重程度减弱且心肌梗死面积进一步减小。结果表明，SM能加强IP的心肌保护作用，特别是加强IP的抗心肌梗死作用。     

Identification of Candidate Long Noncoding RNAs Associated with Left Ventricular Hypertrophy

Purpose

Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.

Methods

Wild‐type and adenosine A2A receptor overexpressing mice (A2A‐Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome‐wide microarrays and an analytical pipeline specifically developed for lncRNAs.

Results

Microarray analysis identified two lncRNAs up‐regulated and three down‐regulated in the hearts of A2A‐Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A‐Tg mice (3.5‐ and 1.8‐fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham‐operated animals (1.8‐ and 1.4‐fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2‐ and 1.6‐fold (p < 0.01).

Conclusions

First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart.     

Mitochondrial Potassium Channels as Pharmacological Target for Cardioprotective Drugs

Brief periods of ischemia are known to confer to the myocardium an increased resistance to the injury due to a later and more prolonged ischemic episode. This phenomenon, known as ischemic preconditioning (IPreC), is ensured by different biological mechanisms. Although an exhaustive comprehension of them has not been reached yet, it is widely accepted that mitochondria are pivotally involved in controlling cell life and death, and thus in IPreC. Among the several signaling pathways involved, as triggers and/or end effectors, in the mitochondrial mechanisms of cardioprotection, an important role is played by the activation of potassium channels located in the mitochondrial inner membrane (mitoK) of cardiomyocytes. Presently, different types of mitoK channels have been recognized in the heart, such as ATP‐sensitive (mitoK_ATP) and calcium‐activated (mitoBK_Ca and mitoSK_Ca) potassium channels. Consistently, drugs modulating mitoK, on one hand, have been employed as useful experimental tools for early basic studies on IPreC. On the other hand, activators of mitoK are promising and innovative therapeutic agents for limiting the myocardial injury due to ischemic episodes. In this review, we report the experimental evidence supporting the role of mitoK in signaling pathways in the mechanisms of cardioprotection and an overview on the most important molecules acting as modulators of these channels, with their profiles of selectivity. Some innovative pharmaceutical strategies for mitochondriotropic drugs have been also reported. Finally, an appendix describing the main experimental approaches usually employed to study mitoK in isolated mitochondria or in intact cells has been added.     

盐酸氟桂利嗪对大鼠离体心脏的保护作用

目的探讨盐酸氟桂利嗪对离体大鼠心脏心功能的影响及对缺血再灌注后心脏的保护作用。方法用Langendorff装置观察盐酸氟桂利嗪对冠脉灌流量及左心室压力的影响及对缺血25 min,再灌注30 min后心脏功能的影响。结果盐酸氟桂利嗪在10-5mol/L时明显增加冠脉灌流量,达10-3mol/L时左室收缩压明显降低。与对照组比较,在缺血前应用10-5mol/L及10-3mol/L的盐酸氟桂利嗪可以改善缺血再灌注后的心功能。结论盐酸氟桂利嗪具有明显的扩冠作用,大剂量可降低心脏收缩功能,应用合适的剂量,对缺血再灌注心脏具有保护作用。     

茵栀黄对高胆红素血症新生儿心肌损伤的保护作用

目的：通过观察高胆红素血症新生儿心肌肌钙蛋白Ⅰ（cTnⅠ）的浓度变化，探讨茵栀黄对高胆红素血症新生儿心肌损伤的保护作用。方法：80例高胆红素血症新生儿随机分为治疗组和对照组。对照组采用常规治疗，包括蓝光照射、补充白蛋白、口服酶诱导剂及纠正酸中毒等处理，治疗组在对照组的基础上，应用茵栀黄注射液治疗。检测治疗前及治疗后7天、14天的cTnⅠ值。结果：与治疗前比较，治疗后7天及14天两组cTnⅠ均有显著降低（P〈0．01）；治疗组在治疗后7天及14天的cTnⅠ降低幅度均大于对照组（P〈0.01）；治疗组黄疸消退时间在7天之内的人数明显增多（χ^2=11．84，P〈0．01）。结论：茵栀黄注射液可缩短高胆血症新生儿黄疸持续时间，降低心肌肌钙蛋白Ⅰ，对心肌损伤具有显著的保护作用。     

Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic peptide: a brief review

1. If one was to design a hormone to protect the heart, it would have a number of features shown by the cardiac natriuretic peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). These hormones are made in cardiomyocytes and are released into the circulation in response to atrial and ventricular stretch, respectively. Atrial natriuretic peptide and BNP can reduce the preload and after-load in normal and failing hearts. They reduce blood volume over the short term by sequestering plasma and over the longer term by promoting renal salt and water excretion and by antagonizing the renin-angiotensin-aldosterone system at many levels. Each of these actions affords indirect benefit to a volume- or pressure-threatened heart. 2. Recent studies have identified additional modes of action of the natriuretic peptides that may also confer cardioprotective benefits, especially in heart disease. The emerging findings are: (i) that ANP and BNP antagonize the cardiac hypertrophic action of angiotensin II and continue working under conditions where endothelial nitric oxide (NO) function is compromised, such as in the presence of high glucose in diabetes; (ii) they potentiate the bradycardia caused by inhibitory ('autoprotective') cardio-cardiac reflexes; and, furthermore, (iii) BNP can suppress cardiac sympathetic nerve activity in humans, including those with heart failure. Thus, it appears that natriuretic peptides can shift sympathovagal balance in a beneficial direction (away from the sympathetic). The vagal reflex and antihypertrophic actions of the peptides are mediated by particulate guanylyl cyclase (pGC) natriuretic peptide receptors. 3. The multiple synergistic actions of the natriuretic peptides make them and their pGC receptors attractive targets for therapy in heart disease. Encouragingly, exogenous natriuretic peptides remain effective even when endogenous peptide levels are raised, as is the case in heart failure. They also remain effective in disease states where other protective mechanisms, such as the NO system, have become ineffective, offering yet further encouragement for the therapeutic use of the natriuretic peptides.     

吗啡后处理对大鼠心肌缺血再灌注损伤的保护作用

目的探讨吗啡后处理对在体大鼠心肌缺血／再灌注损伤的保护作用。方法32只健康雄性SD大鼠随机分配至4个组（n=8）。假手术组（Sham组）：冠脉左前降支只套线,不结扎;缺血再灌注组（I／R组）：再灌注前5min给盐水1ml／kg;吗啡后处理组（MOR组）：再灌注前5min给予吗啡0．3mg／kg;缺血预处理组（IPC组）：先缺血5min再开放5min,反复3次,再进行冠状结扎。建立大鼠心肌缺血30min,再灌注120min动物模型,以血流动力学、心肌酶学、心肌梗死面积、心肌形态学为指标探讨吗啡后处理对再灌注心肌的作用。结果MOR组与IPC组可以降低缺血再灌注损伤引起的心肌酶学增高、显著降低心肌梗死面积（与I／R组比较,P〈0．05）。光学显微镜下I／R组呈现典型的心肌结构病理改变,MOR组和IPC组病理损伤程度较I／R组减轻。结论吗啡后处理可以减轻在体大鼠心肌缺血再灌注损伤,其心肌保护效果与缺血预处理相似。     

Cardioprotective effect of β-d-mannuronic acid (M2000) as a novel NSAID on gene expression of oxLDL scavenger receptors in the experimental diabetic model

Context: The investigations have shown that patients with diabetes have the elevated levels of glucose and oxLDL. These two play an important role in increased expression levels of oxLDL scavenger receptors on the surface of macrophages and endothelial cells that leads to deposition of oxLDL and macrophages in vascular walls.

Objective: The present study intends to show the effects of β-d-mannuronic acid (M2000) on the expression profile of ox-LDL scavenger receptors (including SR-A, LOX-1, CD36, and CD68) in an experimental model of diabetes.

Materials and methods: Eighteen Sprague-Dawley rats were randomly divided into three 6-member groups of the healthy control, diabetic control, and treated rats by M2000. Diabetes was induced in rats by intraperitoneal (IP) administration of 60?mg/kg streptozotocin. The treated rats were given daily intraperitoneal injections of M2000 with a dose of 25?mg/kg for 28 days and at the end of the 28th day, their aortas were removed. The qRT-PCR technique was then used to evaluate the expression levels of the proposed gene.

Results: The gene expression levels of the SR-A, LOX-1, CD36, and CD68 significantly declined in the diabetic group that received M2000 compared with untreated diabetic rats.

Conclusions: The M2000, as a novel NSAID is able to modify by lowering the gene expression levels of SR-A, LOX-1, CD36, and CD68 in treated rats compared to the untreated diabetic group, which may play an important role in preventing the complications that could lead to a cardioprotective efficacy.