Sirt2的结构功能及其在心血管疾病中的作用机制

Sirtuin家族是人体中重要的功能蛋白质,其中Sirt2蛋白的作用还不是十分明了,但近些年来,已有许多研究分析了Sirt2蛋白的结构及功能,已基本阐明其在细胞层面和机体代谢水平的重要作用机制。如果Sirt2蛋白不能正常表达,会诱发或加重心血管疾病。该篇综述重点分析了Sirt2蛋白的作用机制及病理情况,综合整理了现今的最新研究成果,便于之后的临床应用,为相关心血管病的诊断和治疗提供新思路。     

Notch1信号通路在胶质瘤中的作用机制

目的探讨Notch1信号通路在人脑胶质瘤中的作用机制。方法应用实时荧光量(real-time)PCR方法检测50例人脑胶质瘤标本和10例正常脑组织中的Notch1及其下游靶基因Hes1以及增殖指标Ki-67及PCNA的mRNA表达。利用Western印迹检测Notch1的活化片段NICD的表达。结果 Notch1 mRNA在人脑胶质瘤和正常脑组织中均可表达,但在人脑胶质瘤中的表达显著高于正常脑组织(P<0.01),随着胶质瘤恶性程度的增高,Notch1及其下游靶基因Hes1的表达也随之升高,两者的变化趋势一致。Ki-67在胶质瘤中的表达升高,与正常脑组织对比差异显著(P<0.01);PCNA在人脑胶质瘤中的表达同样升高,与正常脑组织对比差异显著(P<0.05)。结论 Notch1信号通路可能通过Hes1作用于胶质瘤细胞,促进细胞的增殖,进而参与到肿瘤的形成及恶化。     

柚皮素通过抑制Sirt1/AMPKα信号通路减轻乙醇诱导的小鼠肝脏脂肪变性

目的:观察柚皮素(NAR)对乙醇诱导的小鼠肝脏脂肪变性的影响并探讨机制。方法:50只雄性KM小鼠随机分为5组，包括Control组、乙醇诱导组(EtOH组)、NAR治疗组(EtOH+NAR组)、NAR溶剂组(EtOH+vehicle组)、NAR联合白藜芦醇(RES)治疗(EtOH+NAR+RES组),每组小鼠10只。苏木精伊红染色观察肝脏脂肪质沉积积累变化，Western Blot分析沉默信息调节因子1(Sirt1)/腺苷酸活化蛋白激酶α(AMPKα)信号通路蛋白表达。细胞实验中，HepG2细胞分为RES组、NAR联合RES组(NAR+RES组)和阴性对照组(NC组)。透射电子显微镜观察脂肪质沉积积累。qRT-PCR检测脂肪合成标志物SREBP1、FASN、ACC、SCD1和脂肪酸β氧化标志物PPARα、CPT1α、UCP2的mRNA表达水平。结果:动物实验中，与Control组比较，EtOH组小鼠的肝组织胎质量明显增加(P<0.05),Sirt1和p-AMPKα(Thr172)蛋白水平明显增高(P<0.05)。与EtOH+vehicle组比较，EtOH+NAR组小鼠的肝脏...     

脂多糖在人缺氧诱导心肌细胞凋亡中的作用及相关机制

目的探讨脂多糖在人缺氧诱导心肌细胞凋亡中的作用及机制。方法收集在该院行风心病换瓣手术的患者二尖瓣乳头肌组织,分离、纯化得到心肌细胞;分别用40、60μg/ml脂多糖预处理心肌细胞6 h,设置空白对照;在37℃、3%O2、5%CO2、95%N2缺氧条件下培养24 h;原位末端标记(TUNEL)法测定凋亡细胞。分别与脂多糖处理前后、缺氧诱导后采用qRT-PCR检测细胞中miR-211表达情况,Western印迹检测细胞中Sirt1蛋白水平。结果缺氧条件下培养24 h后,脂多糖组心肌细胞凋亡率明显高于对照组,60μg/ml脂多糖组明显高于40μg/ml脂多糖组(均P<0.05)。脂多糖处理前,3组细胞中miR-211、Sirt1相对表达量差异无统计学意义(P>0.05);脂多糖处理6 h和缺氧诱导后,40、60μg/ml脂多糖组细胞中miR-211相对表达量均明显高于同期对照组和脂多糖处理前,Sirt1蛋白相对表达量均明显低于同期对照组(均P<0.05),其中60μg/ml脂多糖组变化更明显。结论脂多糖可加速缺氧诱导的心肌细胞凋亡,其作用机制与上调miR-211表达及抑制Sirt1蛋白表达有关。     

心肌营养素-1在心室重塑中的作用

在某些病理条件下，可促使心肌细胞肥大，成纤维细胞增生，胶原合成，最终导致心室重塑。近年有研究发现：心肌营养素-1，作为心脏正常发育过程中必不可少的一个因子，当其过度表达时，参与调节心室肥厚，对心室重塑起作用。     

白藜芦醇-Sirt1 Foxo1调控通路对缺氧心肌细胞的保护作用

目的 研究白藜芦醇-Sirt1-Foxo1调控通路对缺氧心肌细胞的保护作用。方法 将大鼠心肌细胞株H9C2培养48 h后,随机分为5组,即20 μmol/L白藜芦醇(resveratrol,Res)干预组、二甲基亚砜（dimethyl sulfoxide,DMSO）对照组、40 mmol/L尼克酰胺（nicotinamide,Nam）干预组、Nam空白对照组及正常对照组。培养24 h后终止培养,用RT-PCR法和免疫细胞化学染色法检测Sirt1、Foxo1、p27、Bim mRNA及其蛋白表达水平的变化;用TUNEL法及流式细胞仪（flow cytometer,FCM）分析细胞凋亡和细胞周期。结果 20 μmol/L Res干预组可使Sirt1 mRNA及SIRT1蛋白表达的水平增加。Sirt1可通过抑制Foxo1 mRNA的转录活性而调节其下游基因p27及Bim的表达。SIRT1的高表达可使细胞周期延长,细胞凋亡减少。结论 Res干预可使SIRT1表达增加。Sirt1可能通过对Foxo1及其下游基因Bim、p27的调控,延长心肌细胞的细胞周期,减少其凋亡。     

Sirt1与糖稳态

持续高血糖是胰岛素抵抗和糖尿病的主要特征,糖稳态失衡引起代谢失调,导致糖尿病及其并发症。Sirt1是哺乳动物中一种NAD依赖性的Ⅲ类组蛋白去乙酰化酶,在能量代谢和胰岛素抵抗中发挥重要作用。Sirt1通过降低PGC-1α、NF-κB、Foxo1、Akt等蛋白分子的乙酰化水平来保护胰岛β细胞功能,提高胰岛素敏感性,改善炎症反应,使机体血糖维持在稳定水平。本文就Sirt1调节糖稳态的最新研究进展进行综述。     

Sirt1 功能的研究进展

Sirt1是迄今为止在哺乳动物细胞中发现的与沉默调控基因Sir2同源性最高的同系物,是一个NAD依赖的去乙酰化酶。它参与了众多基因转录、能量代谢以及细胞衰老过程的调节。Sirt1不仅可以促进脂质动员与肝脏糖异生,还能调控胰岛β细胞的胰岛素分泌功能。此外,Sirt1还是一个内源性的凋亡抑制因子。     

低血糖对心血管疾病预后的影响

糖尿病是心血管疾病的病因之一早已得到共识,在临床上,随着对患者血糖检测和控制不断地加强,低 血糖的发生也在增加,同时低血糖对心血管疾病的影响也引起了更多的关注.本文就低血糖以及血糖的强化控制对心血管疾病预后影响的有关研究进展做一综述,并且对其病理生理机制进行探讨.     

原发性高血压心血管重构的机制及氯沙坦的干预研究

目的　探讨血管内皮功能失调、细胞内钙超负荷与高血压心血管重构的关系及氯沙坦的干预作用。方法　入选原发性轻中度高血压 (EH)伴左室肥厚病人 30例、正常血压 (NT)对照组 30例 ,EH组给予Losartan 5 0～ 10 0mg/d治疗 40周 ,治疗前后检测左室重量指数 (LVMI)、颈总动脉内膜中层厚 (IMT)、血管内皮依赖舒张功能、血清一氧化氮(NO)、血浆内皮素 (ET)、淋巴细胞胞浆内游离钙 ([Ca2 ]i)等项目。结果　治疗前EH组病人IMT、血浆ET、[Ca2 ]i均显著性增加 ,而血流介导血管舒张 (FMD)、血清NO则显著减少 ;治疗后LVMI、IMT、血浆ET、[Ca2 ]i均显著性减少 ,而FMD、血清NO则显著性增加。结论　除肾素 -血管紧张素系统 (RAS)外 ,血管内皮功能失调与细胞内钙超负荷可能是影响高血压心血管重构的重要环节。     

SP600125对1型糖尿病小鼠颈动脉内皮功能及单核细胞趋化蛋白1表达的影响

目的探讨c-Jun氨基末端激酶(JNK)特异性抑制剂SP600125对1型糖尿病小鼠颈动脉内皮功能及单核细胞趋化蛋白1表达的影响。方法本研究分5组。第1组为C57BL/6野生型雄性小鼠,喂养8周;第2组为INS2AK ITA雄性小鼠,每日腹腔注射生理盐水50μL,共8周;第3、4、5组为INS2AK ITA雄性小鼠,每日各腹腔注射SP600125 10、20和30 mg/kg;连续8周。8周后麻醉处死动物,取静脉血检测血清髓过氧化物酶、丙二醛、一氧化氮、一氧化氮合酶;取双侧颈总动脉分别行凝胶迁移或电泳迁移率实验检测颈动脉信号转导子和转录激活子1活性,行W estern b lot检测p-JNK、JNK、单核细胞趋化蛋白1蛋白表达,行免疫组化检测颈动脉内皮单核细胞趋化蛋白1表达。结果与野生型雄性小鼠相比,1型糖尿病小鼠血清髓过氧化物酶、丙二醛明显增高,而血清一氧化氮合酶、一氧化氮明显减低(P<0.01)。给予1型糖尿病小鼠SP600125不同剂量干预后,髓过氧化物酶浓度较1型糖尿病组明显减低,而一氧化氮、一氧化氮合酶浓度明显增高,且SP600125剂量越高,一氧化氮、一氧化氮合酶浓度增加越明显(P<0.05)。...     

microRNA与心血管疾病

microRNA(miRNA)是一类广泛存在于真核生物长度为21～25nt的非蛋白质编码单链RNA,通过与靶基因mRNA分子的3’端非编码区域(3’UTR)互补配对后降低mRNA分子稳定性和翻译抑制两种方式参与靶基因表达调控,在发育、凋亡、代谢以及人类疾病方面都起着不容忽视的作用。新近研究表明,miRNA在心血管疾病中发挥重要的作用,而维持和恢复心脏等靶器官中相应miRNA的稳定表达可能成为心血管等疾病治疗的一个新靶点。深入研究microRNA可能为心血管疾病的诊断和治疗带来全新的方法。     

前列地尔对糖尿病大鼠心功能的保护作用及相关机制

目的观察前列地尔即前列腺素E1(PGE1)对糖尿病大鼠心功能的影响,探讨其对心功能的保护作用及相关机制。方法 50只SD大鼠随机选取10只作为对照组,给予普通饲料喂养;其余40只高糖高脂饲料喂养4周后一次性腹腔注射0.1%链脲佐菌素建立糖尿病模型,造模成功后随机分为模型组、PGE1低剂量组、PGE1中剂量组和PGE1高剂量组。PGE1低、中、高剂量组分别给予前列地尔注射液0.5、1.0、2.0μg/kg每天1次腹腔注射,对照组及模型组给予相应体积的生理盐水腹腔注射。连续给药8周后进行各项指标检测:血清转化生长因子β1(TGF-β1)、血浆N末端B型脑钠肽原(NT-pro BNP)、糖化血红蛋白(Hb A1c);Masson三色染色检测心肌组织胶原容积分数(CVF);Western blot检测心肌组织信号通路相关蛋白TGF-β1、Smad3、Smad7的表达情况。结果与对照组相比,模型组大鼠血清TGF-β1、血浆NT-pro BNP、Hb A1c浓度及CVF值明显升高,心肌组织内TGF-β1、Smad3蛋白含量显著上升,Smad7表达量明显下降(均P0.01)。与模型组比较,PGE1中、高剂量组血清TGF-β1、血浆NTpro BNP浓度及心肌CVF明显下调,心肌TGF-β1、Smad3蛋白表达水平亦明显下调,Smad7的表达量则回升(均P0.01);PGE1高剂量组上述改变更明显。PGE1低剂量组与模型组比较各指标差异无统计学意义。结论前列地尔具有抑制糖尿病大鼠心肌纤维化、改善心功能的作用,其机制与调节TGF-β1/Smad信号转导通路有关。     

Mortality from Cardiovascular Diseases in the Elderly: Comparative Analysis of Two Five-year Periods

Background

Cardiovascular diseases are the leading cause of death in Brazil. The better understanding of the spatial and temporal distribution of mortality from cardiovascular diseases in the Brazilian elderly population is essential to support more appropriate health actions for each region of the country.

Objective

To describe and to compare geospatially the rates of mortality from cardiovascular disease in elderly individuals living in Brazil by gender in two 5-year periods: 1996 to 2000 and 2006 to 2010.

Methods

This is an ecological study, for which rates of mortality were obtained from DATASUS and the population rates from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística). An average mortality rate for cardiovascular disease in elderly by gender was calculated for each period. The spatial autocorrelation was evaluated by TerraView 4.2.0 through global Moran index and the formation of clusters by the index of local Moran-LISA.

Results

There was an increase, in the second 5-year period, in the mortality rates in the Northeast and North regions, parallel to a decrease in the South, South-East and Midwest regions. Moreover, there was the formation of clusters with high mortality rates in the second period in Roraima among females, and in Ceará, Pernambuco and Roraima among males.

Conclusion

The increase in mortality rates in the North and Northeast regions is probably related to the changing profile of mortality and improvement in the quality of information, a result of the increase in surveillance and health care measures in these regions.     

Preliminary Report of Cardiac Study: Cross-Sectional Multicenter Study on Dietary Factors of Cardiovascular Diseases

The International cooperative ‘Cardiovascular Diseases and Alimentary Comparison Study’ (CARDIAC Study) was designed to study the relationship of dietary factors to blood pressure (BP) and other major cardiovascular diseases (CVD) in widely different populations of both industrialized and developing countries. The primary aim of the research was to test specific hypotheses linking the intake of certain dietary constituents, e.g., sodium (Na), potassium (K), calcium (Ca) and protein, to BP (‘Core’ Study); in some centers the relationship between dietary factors and mortality from CVD was also examined (‘Complete’ Study). The final aim of this multicenter research was to contribute to the scientific information base required to guide the formulation of dietary goals for the primary prevention of major CVD. Forty centers in 20 countries are now participating in the CARDIAC Study. From each population 100 males and 100 females aged 50–54 years were selected randomly for BP measurement by an automated system, 24-hour urine collection by aliquot cups, blood sampling etc. according to CARDIAC protocol; and all samples were analyzed by the WHO Collaborating Center (Izumo) by standardized methods. Although studies are now in progress, surveys in China, Tanzania, USSR and Japan suggest the importance of Na and protein intakes, and all data so far obtained of systolic and diastolic BPI urinary Na and K excretions, serum cholesterol levels, etc. show wide distribution in different populations, so that dietary factors of CVD will be analyzed in more detail when the analyses of total samples are completed.     

Equity and Prevention of Cardiovascular Diseases in Latin America and the Caribbean

Non-communicable diseases, particularly cardiovascular diseases, are the leading cause of decreased life expectancy and death in Latin America and the Caribbean. Although a lifestyle, which includes no tobacco use, good nutrition, and regular physical activity is touted as key to health, the environmental, racial, social and economic conditions, which underpin lifestyle are often ignored or considered only secondarily. Placing the main responsibility on a patient to change their lifestyle or to simply comply with pharmacological treatment ignores the specific conditions in which the individual lives. Furthermore, there are major disparities in access to both healthy living conditions as well as access to medical care.There is sufficient evidence to support advocating for policies that support healthy living, particularly healthy food choices. Progress is being made to improve the food environment with enactment of front of package nutritional labels. However, policies were enacted only after intense regional research and advocacy supporting their implementation.Government officials must rise above the pressures of commercial interests and support health-promoting policies or be exposed as self-interest groups themselves. Strong advocacy is required to persuade officials that all policies should take health into consideration both to improve lives and economies.     

内皮微颗粒与心血管疾病的临床评估

内皮微颗粒是从激活或者凋亡的内皮细胞表面脱落的无核囊泡样结构,通过表面蛋白分子介导体内生物过程中的信息传导,其释放受到体内多种因素的精密调节,在心血管疾病发生发展过程中起着重要的作用.本文将对内皮微颗粒的结构、功能及其与心血管疾病的关联,尤其是内皮微颗粒在心血管疾病风险评估、监测和治疗中的临床意义,并结合目前研究进展做一综述.     

线粒体电压依赖性阴离子通道与心血管疾病

电压依赖性阴离子通道(VDAC)是位于线粒体外膜的通道蛋白,是线粒体与细胞质之间转运ATP以及其他代谢产物的主要通道,在线粒体代谢和细胞生长中发挥重要调控作用.近期研究发现,在心肌缺血再灌、糖尿病、心衰、高血压和动脉粥样硬化时,VDAC表达明显增加,引起细胞内钙离子循环紊乱、氧化应激,进而导致细胞凋亡,已成为心血管疾病研究的新热点.本文就VDAC的分子功能,调控及其在心血管疾病中的作用和相关机制进行综述.