不同低氧方式对大鼠血清和组织局部肾素血管紧张素系统的影响

目的 研究慢性间歇低氧(CIH)与持续低氧(CH)对大鼠血清及组织器官局部的肾素血管紧张素(RAS)系统的影响,以探讨CIH相关性高血压及低氧性肺动脉高压的发生机制.方法 18只SD雄性大鼠按随机数字表法分为CIH组、CH组和对照组共3组,每组6只.CIH组大鼠循环给予氮气和压缩空气(每循环180 s,舱内最低氧浓度达6％～8％,维持20～25 s,然后恢复至21％,7 h/d),CH组持续给予氮气(舱内氧浓度保持8％～12％,7 h/d),对照组大鼠常规饲养.结果 第6周时CIH大鼠收缩压(SBP)显著高于CH组、对照组(P＜0.05)和实验前水平(P＜0.01).CIH分别与CH和对照组比较:肾小动脉和肺小动脉中ACE及ACE2水平差异有统计学意义(P＜0.05);血清和肾组织中AngⅡ显著增高(P＜0.05),Ang-(1-7)则明显降低(P＜0.05).CH组肺组织AngⅡ较CIH及对照组增高(P＜0.05),Ang-(1-7)降低(P ＜0.05);SBP与血清及肾AngⅡ水平呈正相关;与Ans-( 1-7)水平呈负相关.CIH组肾小动脉及CH组肺小动脉管壁厚度、壁厚度占外径或内径的百分比(WT％)及管壁面积占血管壁总面积的百分比(WA％)分别与其他两组比较均有明显差异(P＜0.05).肺及肾的小动脉管壁厚度与其相应组织局部的AngⅡ呈正相关(r=0.386、0.414,均P＜0.05),与Ang-( 1-7)呈负相关(r=-0.401,-0.394,均P＜0.05).结论 CIH与CH两种低氧方式对大鼠血清及各组织局部的RAS系统影响程度及结果存在差异性,CIH主要影响大鼠肾组织及肾小动脉及体循环RAS系统,与血压增高密切相关;CH主要影响肺组织及肺小动脉RAS系统,可能与肺动脉重塑及肺动脉高压有关.     

间歇性完全性左束支阻滞13例分析

目的分析间歇性完全左束支阻滞(CLBBB)病例的临床特点。方法回顾分析13例12导联动态心电图检出间歇性完全左束支阻滞患者的病因、动态心电图、超声心动图、冠状动脉造影结果。结果 60岁以上患者12例,占92%。病因以冠心病、高血压、扩张型心肌病多见。本组冠脉造影及冠状动脉螺旋CT血管成像的7例间歇性完全性左束支阻滞患者中确诊为冠心病者3例。超声心动图结果:53.8%患者心房增大或心房心室同时增大。动态心电图检查可见间歇完全左束支阻滞常合并各种类型心律失常。结论间歇完全性左束支阻滞常发生在老年患者,常见于器质性心脏病,尤其是冠心病、高血压、扩张型心肌病。     

鞘氨醇激酶1对结肠癌细胞血管生成拟态的影响及其机制

目的:研究鞘氨醇激酶1(sphingosine kinase1,Sphk1)对人结肠癌HT-29细胞生成血管拟态(vasculogenic mimicry,VM)的影响及其可能的机制.方法:将人结肠癌HT-29细胞分为Sphk1抑制组、Sphk1激活组、对照组.Sphk1抑制组加入N,N-二甲基鞘氨醇(N,N-dimethyl-D-erythro-sphingosine,DMS)50μmol/L;Sphk1激活组加入佛波醇-12-豆蔻酸酯-13-乙酸酯(phorbol12-myristate-13-acetate,PMA)100nmol/L;对照组加入等量的培养基.采用MTT法检测细胞生长增殖;透射电镜观察细胞形态学变化;Matrigel三维培养法观察VM形成能力;Transwell小室模型观察细胞侵袭迁移能力的变化,QT-PCR、Western blot及ELISA技术检测血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达.结果:DMS显著抑制细胞的增殖、侵袭、迁移并促进细胞凋亡;透射电镜可见典型的凋亡特征;三维培养中不能形成管状VM;明显减弱VEGFmRNA及蛋白表达.PMA则显著促进HT-29细胞的增殖、侵袭、迁移并抑制细胞的凋亡;透射电镜可观察到细胞增殖特征;促进三维培养中管状VM的形成;明显增强VEGFmRNA及蛋白表达.对照组、DMS组及PMA组的侵袭细胞数:112.00±6.25vs57.00±8.00,142.00±5.57;迁移细胞数:69.33±4.04vs42.00±4.16,111.00±8.03;VEGFmRNA表达量:1.000vs0.740±0.122,1.220±0.075;VEGF蛋白表达:0.39±0.05vs0.23±0.02,0.65±0.06;VEGF蛋白分泌:103.00±8.96vs63.89±8.44,201.01±17.93,均P<0.05.结论:Sphk1可促进HT-29细胞增殖、侵袭、迁移并抑制细胞的凋亡,诱导VM的形成,其机制可能是通过增强结肠癌细胞的侵袭迁移能力并促进VEGF表达而发挥作用.     

Variability in hemoglobin A1c predicts all-cause mortality in patients with type 2 diabetes

BackgroundTo evaluate the relationship between hemoglobin A1c variability and all-cause mortality in type 2 diabetic patients.MethodsThis was a retrospective cohort study in type 2 diabetic patients followed for at least 2 years between 2003 and 2009. A1C variability was determined from the standard deviation or coefficient of variation of serial A1C values (A1C_SD or A1C_CV). Subjects were categorized into either the high or low A1C variability group according to their A1C_CV median. Hazard ratios (HRs) of various factors for all-cause mortality were determined from Cox's proportional hazard models.ResultsA total of 881 subjects (422 men, 459 women) were included and 73 (8.3%) died during follow-up. The follow-up period was 4.7 ± 2.3 years. All-cause mortality was higher in subjects with high A1C_CV (11.0% vs. 5.4%, p = 0.002). In the Kaplan–Meier failure curve, subjects with higher A1C_CV demonstrated a trend of higher mortality (p = 0.1). In multivariate Cox's proportional hazards models, A1C_SD and A1C_CV significantly predicted all-cause mortality with an HR of 1.987 (p = 0.02) and 1.062 (p = 0.013), respectively, after adjusting for age, gender, body mass index, duration of diabetes, mean systolic blood pressure, use of antihypertensives and statins, mean LDL-cholesterol, smoking status, chronic kidney disease, and mean A1C values (A1C_MEAN). The ability of A1C_SD and A1C_CV to predict all-cause mortality was more evident in subjects with relatively low A1C_MEAN.ConclusionsA1C variability is an important risk factor for all-cause mortality in type 2 diabetic patients.     

The influence of network structure on the transport of blood in the human cerebral microvasculature

In this article, we explore how the structural properties of miniature networks influence the transport of blood through the human cerebral microvasculature. We propose four methods for generating such networks, and investigate both how the resulting network properties match available experimental data from the human cortex and how these properties affect the flow of blood through the networks. As the nature of such microvascular flow patterns is inherently random, we run multiple simulations. We find that the modified spanning tree method produces artificial networks having characteristics closest to those of the microvasculature in human brain, and also allows for high network flow passage per unit material cost, being statistically significantly better than three other methods considered here. Such results are potentially extremely valuable in interpreting experimental data acquired from humans and in improving our understanding of cerebral blood flow at this very small length scale. This could have a significant impact on improving clinical outcomes for vascular brain diseases, particularly vascular dementia, where localized flow patterns are very important.     

Advanced glycation end-products induce injury to pancreatic beta cells through oxidative stress

AimThis study evaluated the direct effects of advanced glycation end-products (AGEs) on pancreatic β cells, including cellular viability, generation of reactive oxygen species (ROS) and insulin secretion, and also looked for the main source of ROS in INS-1 cells and the possible molecular mechanism(s) of cell injury by AGEs.MethodsINS-1 cells were cultured with 100, 200 and 500 mg/L of AGEs for specific periods of time. Cell apoptosis was determined by ELISA and real-time PCR assays. ROS were detected by DCFH-DA and MitoSOX Red probes with a flow cytometer, NADPH oxidase activity was measured by lucigenin chemiluminescence and MAPK phosphorylation was measured by Western blot tests.ResultsBoth cell apoptosis and ROS generation increased in AGE-treated cells in a dose-dependent way, and both the mitochondrial electron transport chain and NADPH oxidase pathway participated in ROS generation, although the role of the mitochondrial pathway was earlier and more important. AGEs exerted a toxic effect on insulin secretion that could be largely reversed by inhibiting ROS.ConclusionAGEs injured INS-1 cells by oxidative stress mainly through the mitochondrial pathway, although the JNK and p38 MAPK signaling pathways were also key modulators in ROS-mediated β-cell death.