二甲双胍的心脏保护作用

二甲双胍是临床上广泛应用的治疗2型糖尿病的药物。近年来不断有证据表明二甲双胍具有心脏保护作用,可提高心肌供能,促进一氧化氮的合成,改善胰岛素抵抗、抗炎、抗纤维化,抑制心肌细胞凋亡。同时研究显示二甲双胍的药理作用是通过激活腺苷激活的蛋白激酶实现。腺苷激活的蛋白激酶是一种重要的激酶,在调节糖脂代谢方面发挥着重要作用。     

Post–conditioning reduces infarct size in the isolated rat heart: Role of coronary flow and pressure and the nitric oxide/cGMP pathway

We aimed to assess the role of the nitric oxide (NO)–cGMP pathway in cardioprotection by brief intermittent ischemias at the onset of reperfusion (i.e., post–conditioning (Post–con)). We also evaluated the role of coronary flow and pressure in Post–con. Rat isolated hearts perfused at constant– flow or –pressure underwent 30 min global ischemia and 120 min reperfusion. Post–con obtained with brief ischemias of different duration (modified, MPost–con) was compared with Post–con obtained with ischemias of identical duration (classical, C–Post–con) and with ischemic preconditioning (IP). Infarct size was evaluated using nitro–blue tetrazolium staining and lactate dehydrogenase (LDH) release. In the groups, NO synthase (NOS) or guanylyl–cyclase (GC) was inhibited with LNAME and ODQ, respectively. In the subgroups, the enzyme immunoassay technique was used to quantify cGMP release. In the constant–flow model, M–Post–con and C–Post–con were equally effective, but more effective than IP in reducing infarct size. The cardioprotection by M–Post–con was only blunted by the NOS–inhibitor, but was abolished by the GC–antagonist. Post–ischemic cGMP release was enhanced by MPost–con. In the constant–pressure model IP, M–Post–con and C–Post–con were equally effective in reducing infarct size. Post–con protocols were more effective in the constant–flow than in the constant–pressure model. In all groups, LDH release during reperfusion was proportional to infarct size. In conclusion, Post–con depends upon GC activation, which can be achieved by NOS–dependent and NOS–independent pathways. The benefits of M– and CPost–con are similar. However, protection by Post–con is greater in the constant–flow than in the constant–pressure model.     

Percutaneous endocardial injection of erythropoietin: assessment of cardioprotection by electromechanical mapping

BACKGROUND: Apart from its well-known stimulation of erythropoiesis, erythropoietin (EPO) exhibits angiogenic and anti-apoptotic effects. These cellular protective effects have also been described in experimental acute myocardial infarction models. We investigated the effects of EPO in a porcine model of chronic progressive myocardial ischaemia. METHODS: At weeks 2 and 6 after implantation of a circumflex ameroid constrictor, endocardial electromechanical NOGA system (Biosense Webster, Inc., California, USA) mapping of the left ventricle, coronary and ventricular angiography, as well as echocardiography were performed. Two weeks after ameroid placement, 13 pigs were randomized with 7 pigs receiving 10.000 U EPO and 6 pigs receiving placebo into the ischaemic region using a NOGA guided percutaneous transendocardial injection catheter, MYOSTAR. After 6 weeks, histology (Masson's Trichrome) was analyzed. RESULTS: Endocardial electromechanical mapping showed an increase of mean unipolar voltage (UV) amplitude in the ischaemic myocardial segments in the EPO-treated animals (8.5 mV pre and 10.6 mV post treatment) and a significantly reduced ischaemic surface area compared to the control group (19% vs. 41%) suggesting a decline in ischaemic injury. Echocardiography revealed 2,2 hypokinetic segments of the lateral wall in the EPO group vs. 3,3 in the control groups. The mean ejection fraction was 64% in the EPO group and 55% in the placebo group. Quantitative histological analysis of the ischaemic regions revealed a reduction of myocardial fibrosis (8% vs. 28%) in the EPO group. CONCLUSION: Endocardial EPO injection may induce cardioprotective effects in hibernating myocardium and may attenuate the progression of ischaemic tissue damage.     

经皮冠状动脉介入术前他汀类药物预治疗：消炎与心肌保护

3-羟基-3-甲基-戊二酰辅酶A（HMG-CoA）还原酶抑制剂（又称他汀类药物）目前已成为冠心病标准治疗药物,在冠心病的一级预防和二级预防中效果显著。最近研究显示,他汀类药物在降脂作用发生前就开始起作用,包括改善血管内皮功能、消炎、心肌保护、减少血小板黏附、稳定动脉粥样硬化斑块等,这种与降脂作用无关的作用称其为多效性。经皮冠状动脉介入术（percutaneous coronary intervention,PCI）相关的心肌损害和炎症是心血管病治疗中的一个并发症。本文就近年来的临床试验,对PCI病人术前他汀类药物预治疗的消炎和心肌保护作用作一回顾。     

Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during ischemic postconditioning by crosstalk with the RISK signaling pathway

Background Ischemic postconditioning （IPost）,able to significantly attenuate myocardial ischemia reperfusion injury,is dependent on RISK signaling.Studies have shown that Notch signaling repairs damaged myocardium,and this study aimed to investigate the effect of Notch signaling in myocardial IPost.Methods We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation （H/R） model in vitro,which were randomly divided into control,H/R,IPost,Hepatocyte growth factor （HGF）＋IPost and DAPT＋IPost,N1ICD＋IPost,miRNA＋lPost,and Mock treatment groups.The myocardial cell viability was assessed by MTT,the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses.The expression of N1ICD,Hes1,PTEN Phospho-Akt/Akt,Phospho-GSK-3β/GSK-3β were detected by Western blotting.Finally,we assessed the changes in Ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.Results The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost,which increased myocardial cell viability,prevented cardiomyocyte apoptosis,and reduced loss of the mitochondrial membrane potential.However,myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA.Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated,which consequently promoted Akt and GSK-3β phosphorylation.Conclusions Notch1 crosstalk with RISK signaling may be dependent on PTEN,which plays a cardioprotective role during IPost.This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.     

呫吨酮类化合物的药理作用研究进展

呫吨酮类化合物在自然界中广泛存在,它及其衍生物具有广泛的生理学和药理学活性,具有抗肿瘤、保护心血管、降低血糖、抗氧化、抗菌等药理作用,但很多药理作用机制尚处于研究探索阶段,从而使其药理活性及其与构型关系的研究倍受关注.收集国内外近几年来的有关文献,综述呫吨酮类化合物的药理研究进展.     

腺苷A1受体激动剂预处理兔延迟相心肌蛋白质组学分析

目的:研究腺苷A1受体激动剂2-氯环戊腺苷(2-chloro-N6-cyclopentyladenosine,CCPA)预处理延迟相缺血再灌注心肌保护的蛋白质表达谱的变化.方法:8只新西兰大白兔随机分为CCPA预处理组(CCPA组)和生理盐水预处理组(NS组).CCPA组用100 μg/kg CCPA预处理大白兔,NS...