LncRNA SNHG1 promotes sepsis‐induced myocardial injury by inhibiting Bcl‐2 expression via DNMT1

Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)‐mediated DNA methyltransferase 1/B‐cell lymphoma‐2 (DNMT1/Bcl‐2) axis in sepsis‐induced myocardial injury. Mice and HL‐1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed lncRNA in sepsis samples through microarray profiling, and the upregulated expression of lncRNA SNHG1 was confirmed in myocardial tissues of LPS‐induced septic mice and HL‐1 cells. Further experiments suggested that silencing of lncRNA SNHG1 reduced the inflammation and apoptotic rate of LPS‐induced HL‐1 cells. LncRNA SNHG1 inhibited Bcl‐2 expression by recruiting DNMT1 to Bcl‐2 promoter region to cause methylation. Inhibition of Bcl‐2 promoter methylation reduced the inflammation and apoptotic rate of LPS‐induced HL‐1 cells. In vivo experiments substantiated that lncRNA SNHG1 silencing alleviated sepsis‐induced myocardial injury in mice. Taken together, lncRNA SNHG1 promotes LPS‐induced myocardial injury in septic mice by downregulating Bcl‐2 through DNMT1‐mediated Bcl‐2 methylation.     

蒙药绍沙-7味丸防治大鼠心肌缺血/再灌注损伤的作用

目的:探讨蒙药绍沙-7味丸对心肌缺血/再灌注损伤大鼠的防治作用及机制.方法:60只大鼠随机分成6组:假手术组、模型组、蒙药绍沙-7味丸低、中、高剂量组以及阳性药对照组,每组10只;蒙药绍沙-7味丸低、中、高剂量组分别灌胃0.4 g/kg、0.8 g/kg、1.6 g/kg蒙药绍沙-7味丸,阳性药对照组灌胃0.3 g/k...     

实时无标记细胞分析系统 (RTCA) 在药物心肌毒性检测和生物活性研究中的应用

实时无标记细胞分析系统 (Real time xCELLigence analysis system,RTCA) 是一种新型细胞检测技术,能够连续监测、记录及分析细胞活动产生的各种信息,在药物研究中的心肌毒性评估和细胞生物活性考察方面都可以发挥重要作用。文中首先对RTCA的原理与特点进行了介绍,然后分别对RTCA在心肌毒性和细胞生物活性研究中的应用现状进行了综述,为了解和使用RTCA提供了参考。RTCA技术具有实时无标记、非侵入性、高通量、准确性高等特点,不仅有助于药物研究和新药开发,在其他一些领域也有着广阔良好的应用前景。     

自噬在急性心肌梗死发病中作用的研究进展

自噬是生物细胞内普遍存在且高度保守的一种生理过程,其通过溶酶体融合降解细胞内的大分子组分、受损的细胞器以及侵入胞内的病原菌,以达到维持细胞稳态的目的。自噬在多种疾病的发生发展中也发挥十分重要的作用,尤其是心血管疾病。自噬对其病程的发展可以发挥两种截然不同的作用。适当的自噬作用可以降低炎症反应和氧化应激促进细胞的存活,以及通过减少泡沫细胞的形成而对维持心血管的正常功能起一个保护作用;但过度的自噬作用会对细胞造成不可逆的损伤,诱导细胞发生不依赖于caspase的自噬性细胞死亡,增加局部的炎症反应,从而促进动脉粥样硬化病变的发展。本文就自噬在急性心肌梗死发生发展中作用的研究进展进行了综述,探讨自噬成为预防及治疗心血管疾病新靶标的可能性。     

N-乙酰半胱氨酸对大鼠心脏成纤维细胞增殖和胶原合成的影响

目的:通过观察N-乙酰半胱氨酸(NAC)对大鼠心脏成纤维细胞(CFs)增殖和胶原合成的影响,探讨NAC对心脏重构的作用。方法:以培养的新生SD大鼠CFs为实验对象,给予不同浓度的NAC进行干预,48小时后用MTT比色法检测CFs增殖水平,用3H脯氨酸掺入法测定总胶原合成。结果:与对照组相比,不同浓度NAC作用下的CFs增殖水平和3H脯氨酸掺入量均比对照组低,且具有浓度依赖性(p<0.05)。结论:NAC能够抑制SD大鼠CFs增殖,并降低其胶原合成,因此NAC对心脏的病理性重构可能具有保护作用。     

半量瑞替普酶溶栓后行转运PCI与直接转运PCI对急性ST段抬高型心肌梗死临床疗效的对比研究

目的:比较急性ST段抬高型心肌梗死(STEMI)使用半量瑞替普酶溶栓后行转运经皮冠脉介入治疗(PCI)与直接转运两种救治策略的临床效果。方法:回顾性分析2015年6月～2018年2月我院收治的100例STEMI患者的病历资料,根据救治方案不同分为易化PCI组(先在基层医院经半量瑞替普酶溶栓后再转运至我院行PCI,58例)、直接转运PCI组(拒绝在基层医院接受溶栓治疗而要求直接转运PCI,42例)。比较两组PCI前后血管再通率、PCI后无复流发生率和ST段回落率(STR)、住院期间主要不良心脏事件(MACE)及治疗期间出血并发症的发生情况及随访1年主要终点事件的发生情况。结果:入院后首次冠脉造影显示易化PCI组PCI前TIMI 3级血流者占32.7%(19/59),显著高于直接转运PCI组[14.3%(6/42),P0.05]。PCI后14 d时,易化PCI组TIMI 3级血流者占93.1%(54/58),较直接转运PCI组[90.5%(38/42)]差异无统计学意义(P0.05)。PCI后即刻冠脉造影显示易化PCI组无复流发生率为6.9%(4/58),较直接转运PCI组[21.4%(9/42)]显著降低(P0.05)。PCI后24 h时,易化PCI组STR值为(61.53±11.27)%,显著高于直接转运PCI组[(52.40±12.63)%,P0.05]。住院期间,易化PCI组MACE发生率为10.3%(6/58),较直接转运PCI组[14.3%(6/42)]差异无统计意义(P0.05)。治疗期间,易化PCI组出血并发症总发生率为19.0%(11/58),与直接转运PCI组的14.3%(6/42)相比差异亦无统计学意义(P0.05)。随访1年,易化PCI组主要终点事件发生率为19.0%(11/58),显著低于直接转运PCI组[40.5%(17/42),P0.05]。结论:与直接转运PCI相比,STEMI患者应用半量瑞替普酶溶栓后行转运PCI有利于早期开通梗死血管,提高介入干预效果,PCI后获得优异的心肌灌注水平,从而改善远期预后,且安全性相当。     

三七总皂甙和灯盏花素复方注射剂对结扎大鼠冠脉致心肌缺血的保护作用

采用结扎大鼠冠脉造成急性心肌缺血模型 ,观察了三七总皂甙和灯盏花素复方注射剂 (简称复方注射剂 )抗实验性心肌缺血作用。结果表明 :大鼠静脉注射复方注射剂 5 0mg/kg和 10 0mg/kg对急性心肌缺血均有一定程度的保护作用 ,在改善心电图S T段的上移、降低血清CPK、LDH方面两个剂量组均有显著作用 (P <0 .0 5 ,P <0 .0 1)以 10 0mg/kg组缩小心肌梗塞范围为显著 (P <0 .0 5 )。复方注射剂与丹参注射剂均能保护超氧化物歧化酶活性 (P <0 .0 5 ,P <0 .0 1) ,显著降低丙二醛含量 (P <0 .0 1)。复方注射剂两个剂量组均能显著增加前列环素合成 (P <0 .0 5 ,P <0 .0 1)。提示三七总皂甙和灯盏花素复方注射剂对心肌缺血的保护作用与抗脂质过氧化作用有关 ,其促进前列环素合成作用可能与其抗心肌缺血有关。     

Resveratrol,novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

Myocardial ischemia/reperfusion injury (MI/RI) is the main cause of deaths in the worldwide, leading to severe cardiac dysfunction. Resveratrol (RSV) is a polyphenol plant‐derived compound. Our study aimed to elucidate the underlying molecular mechanism of preconditioning RSV in protecting against MI/RI. Mice were ligated and re‐perfused by the left anterior descending branch with or without RSV (30 mg/kg·ip) for 7 days. Firstly, we found that RSV pretreatment significantly alleviated myocardial infarct size, improved cardiac function and decreased oxidative stress. Furthermore, RSV activated p‐AMPK and SIRT1, ameliorated inflammation including the level of TNF‐α and IL‐1β, and promoting autophagy level. Moreover, neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown the expression of AMPK, SIRT1 or FOXO1 were used to uncover the underlying molecular mechanism for the cardio‐protection of RSV. In NRVMs, RSV increased cellular viability, decreased LDH release and reduced oxidative stress. Importantly, Compound C(CpC) and EX527 reversed the effect of RSV against MI/RI in vivo and in vitro and counteracted the autophagy level induced by RSV. Together, our study indicated that RSV could alleviate oxidative stress in cardiomyocytes through activating AMPK/SIRT1‐FOXO1 signallingpathway and enhanced autophagy level, thus presenting high potential protection on MI/RI.     

一氧化氮对心肌缺血/再灌注损伤细胞凋亡和心功能的影响

目的:采取促进或抑制NO的方法,了解在重复可逆性心肌缺血/再灌注所致的心肌顿抑时,血液中一氧化氮(NO)的动态变化与细胞顿抑及心功能的影响.方法:新西兰兔15只,随机分为3组(n=5):对照组、在静脉内注射NO合成底物L-精氨酸为L-Arg组、静脉注射一氧化氮合酶抑制剂L-硝基-精氨酸为L-NNA组.用戊巴比妥钠静脉注射麻醉后,结扎前降支制成心肌缺血/再灌注模型,用电子自旋共振法测定血液中NO含量,同时记录左心室最大上升速率dp/dtmax.将兔心肌缺血10 min,共3次,第1、2次缺血后再灌注10 min,第3次缺血后再灌注120 min.结果:第1次缺血/再灌注5 min时NO升高的顺序依次为L-Arg组最大、对照组次之,而L-NNA组较缺血前降低.而dp/dtmax明显下降的是L-Arg组最大、对照组次之、L-NNA组最小.细胞凋亡指数:L-Arg组最大,对照组次之、L-NNA组最小.结论:再灌注早期NO的大量生成及细胞凋亡参与加重心肌顿抑的过程.     

Elevated lipoprotein(a) as a predictor for coronary events in older men

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5–6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30–50 mg/dl) levels of Lp(a) over 8 years (Gray’s test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0–4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.