DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Immunohistochemical analysis of von Willebrand factor expression in myocardial tissues from autopsies of patients with ischemic heart disease

von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.     

蒙药安神补心六味丸预防给药对心肌缺血大鼠的保护作用及氧化应激水平的影响＊

目的 研究蒙药安神补心六味丸对大鼠心肌缺血损伤的保护作用和氧化应激机制。方法 将60只大鼠随机分为空白组、模型组、阳性对照组（丹参滴丸）及蒙药安神补心六味丸低、中、高剂量组，使用腹腔注射异丙肾上腺素方法制备大鼠急性心肌缺血模型，记录并观察大鼠心电图活动变化，然后进行腹主动脉取血，分离血清，测定乳酸脱氢酶（Lactic dehydrogenase，LDH）、肌酸激酶（Creatine kinase，CK）、磷酸肌酸激酶（Creatine kinase isoenzyme，CK-MB）、谷草转氨酶（Aspartate aminotransferase，AST）、超氧化物歧化酶（Superoxide dismutase，SOD）、丙二醛（Malondialdehyde，MDA）和谷胱甘肽过氧化物酶（Glutathione peroxidase，GSH-PX）含量变化。取心肌组织固定，对大鼠心肌组织进行HE染色，通过对心肌酶学和和心肌组织形态学两个方面来考察蒙药安神补心六味丸对大鼠心肌缺血模型的保护作用。结果 与空白组比较，模型组大鼠血清中LDH活性极显著升高（P<0.01），CK、CK-MB、AST、MDA活性均显著升高（P<0.05），SOD活性显著降低（P<0.05），GSH-PX活性高度显著降低（P<0.001），且差异均具有统计学意义；与模型组比较，蒙药安神补心六味丸组高剂量组大鼠血清中LDH、CK、CK-MB、MDA活性显著降低（P<0.05），SOD活性显著升高（P<0.05），GSH-PX活性极显著升高（P<0.01），且差异均具有统计学意义。从HE染色分析，蒙药安神补心六味丸能够改善因缺血而造成的心肌组织损伤。结论 蒙药安神补心六味丸能有效改善心肌组织病理状态，减轻大鼠心肌缺血损伤，以达到保护心肌作用，机制可能与氧化应激机制相关。     

Serum uric acid in patients with ST-segment elevation myocardial infarction: An innocent bystander or leading actor?

Elevated serum uric acid (SUA) levels have been associated with several cardiovascular risk factors and the progression of coronary artery disease. In the setting of acute myocardial infarction, increasing evidence suggests that high SUA levels could be related to adverse outcomes. Interestingly elevated SUA levels have been linked to endothelial dysfunction, inflammation and oxidative stress. The aim of this review is to discuss the potential negative effects of SUA in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, analyzing the possible underlying pathophysiological mechanisms.     

Impact of repaired aortic coarctation in left ventricular myocardial work

AimsMyocardial strain analysis enables more precise assessment of cardiac performance but is relatively load dependent. New tools have been developed with afterload adjustment. Our objective was to assess myocardial work (MW) in patients with repaired aortic coarctation (rACo).MethodsProspective study of consecutive patients with rACo who underwent a routine transthoracic echocardiogram in 2018 and 2019 at our center. Patients with significant aortic valve disease, pacemaker, or other congenital heart diseases (except for mild bicuspid aortic valve disease) were excluded. Global longitudinal strain with two dimensional speckle tracking analysis and MW were obtained (GWI:Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency). Blood pressure was measured in the patient's right arm.ResultsWe included 42 patients in the analysis, mean age of 37±10 years, 38% males. In this group, 52% had hypertension and 64% had a concomitant bicuspid aortic valve. In comparison to previously published reference values, patients with rACo had significantly lower GWI (1807 vs. 1896 mmHg%) and GCW (2173 vs. 2232 mmHg%) (p<0.001), particularly in males. Systolic blood pressure is an independent predictor for GWI (β=0.432) and for GCW (β=0.534) and GLS an independent predictor of all MW parameters (β>0.594). Neither age nor gender were independent predictors.ConclusionsIn patients with rACo, there are some signs of left ventricular dysfunction with a reduction in GCW and GWI and with preserved GWE, despite normal ejection fraction and strain.     

二维斑点追踪显像技术评估窒息新生儿左心室纵向收缩功能与心肌损害的相关性

【摘要】目的 探讨二维斑点追踪显像技术(2D-STI)评估新生儿窒息合并心肌损害后左心室整体及局部心肌的纵向收缩功能在早期诊断窒息新生儿心肌损害中的临床价值。方法 选择2019年07月至2020年12月期间在右江民族医学院附属医院新生儿科住院的足月窒息新生儿61例，经临床确诊合并心肌损害，根据Apgar评分分为轻度组31例和重度组30例，选择同期住院出生的正常足月新生儿30例作为对照组。检测受检者的血清肌酸激酶同工酶（CK-MB）、肌钙蛋白（cTnT）、左室舒张期前后径（LVDId）、左室射血分数（LVEF）、左室短轴缩短率（LVFS）、辛普森法左室射血分数（Simpson EF）、左室三腔心整体应变（GLS-LAX）、左室四腔心整体应变（GLS-A4C）、左室两腔心整体应变（GLS-A2C）、左室整体应变（GLS-AVG）,分析GLS-AVG和CK-MB、cTnT三者的相关性。结果 三组间CK-MB和cTnT比较差异有统计学意义（P<0.05）。三组间性别、体重、胎龄均无统计学差异（P>0.05）。三组间LVDId、LVEF、LVFS、Simpson EF比较差异无统计学意义（P>0.05）。GLS-AVG与CK-MB呈负性相关（r=-0.515，P=0.000），GLS-AVG与cTnT呈负性相关（r=-0.912，P=0.000）。结论 GLS-AVG与CK-MB、cTnT具有相关性，GLS-AVG可作为窒息新生儿心肌损害早期诊断指标。