大鼠心肌缺血/再灌注损伤及预处理apelin的表达

目的观察大鼠心肌缺血/再灌注损伤及预处理中apelin表达变化,探讨其可能的作用。方法SD大鼠60只随机分成4组:缺血/再灌注组(IR),预处理组(IP),假手术组(SH)和正常对照组(NC)。放免法测定血浆及心肌apelin-36蛋白含量,免疫组化法观察心肌apelin的表达,RT-PCR方法探讨大鼠心肌apelin mRNA表达。结果(1)血浆、心肌组织apelin-36浓度:IR的含量分别比NC低36.1%、45.6%(P<0.01),IP分别比NC低23.8%、24.7%(P<0.01)。SH与NC、IR与IP比无差异(P>0.05)。(2)apelin免疫组化染色吸光度值:IR与IP比NC分别低65.3%和36.8%(P<0.01,P<0.05),IR比IP低45.1%(P<0.05)。SH与NC无差别(P>0.05)。(3)心肌apelin mRNA的水平:IR是NC的40.2%(P<0.01),IP为NC的65.2%(P<0.05),IR是IP组的38.3%(P<0.05),SH与NC无差别(P>0.05)。结论在心肌缺血/再灌注损伤及预处理过程中,大鼠血浆及心肌组织apelin-36蛋白及基因表达下调,提示apelin在该病理生理过程中可能有重要作用。     

Apelin/APJ系统在心血管疾病中的生理与病理作用

Apelin/APJ系统在人体组织中分布广泛,通过自分泌和旁分泌等信号途径发挥重要的生物学效应。它具有调节血管舒缩功能、正性肌力作用、调节血管内皮功能、刺激VSMC表型转换和增殖功能、促进血管发生、调节体液平衡等重要生物学功能,参与动脉粥样硬化、高血压、心力衰竭、心肌梗塞、心房纤颤等多种心血管系统疾病的发生发展。本文对Apelin/APJ系统在心血管疾病中的生理、病理作用进行了综述。     

代谢综合征患者血清Apelin水平增高

探讨代谢综合征(MS)患者血清Apelin的变化.用ELISA法测定血清Apelin.MS组Apelin明显升高(P＜0.01),2型糖尿病MS组Apelin明显高于糖调节受损MS组和超重或肥胖者[(475.8±37.3对451.5±54.3及430.3±52.1)ng/L,P＜0.01].多元逐步回归分析显示,胰岛素抵抗、体重指数和总胆固醇是Apelin独立相关因素.MS多种代谢组分异常与Apelin升高密切相关,可能是胰岛素抵抗加重所致.     

Treatment of Acute Rejection

Abstract

Background: Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in patients with end stage renal disease (ESRD). Apelin expressed in endothelial and other tissues including brain and kidney is an adipocytokine defined recently and is emerging an important mediator of cardiovascular homeostasis. The aim of this study was to test whether apelin levels might be associated with carotid artery atherosclerosis and left ventricular mass index (LVMI) in peritoneal dialysis patients. Patients and methods: Fifty peritoneal dialysis patients (25 female, mean age 41.4?±?11.9 years, mean dialysis vintage 65.0?±?35.4 months) and 18 healthy individuals (9 female, mean age 41.7?±?6.8 years) were included in this cross-sectional study. Serum apelin 12 levels, echocardiographic findings and carotid intima media thickness (CIMT) were recorded as well as clinical and laboratory data. Results: There were no differences between the patient and the control groups with regard to demographic characteristics. In patient group, LVMI, CIMT, CRP and apelin levels were elevated compared to control group. However there was no association between apelin, LVMI and CIMT. There was a positive correlation between apelin and CRP, which was not statistically significant. When patients were divided into two groups according to the mean serum apelin levels, LVMI, CIMT and CRP were higher in the high apelin group but this difference did not reach statistical significance. Conclusion: We observed an increased inflammation and CVD risk in peritoneal dialysis patients. However, serum apelin levels seem not to be associated with cardiovascular risk in this group of patients.     

胰岛素抵抗对大鼠肝脏组织Apelin表达的影响

目的探讨胰岛素抵抗（insulin resistance IR）对大鼠肝脏组织Apelin蛋白表达的影响。方法 16只雄性SD大鼠随机分两组：IR组和对照组,每组8只。取肝脏组织进行Apelin免疫组化染色,测定平均光密度值。结果 Apelin平均光密度值：IR组高于对照组,P〈0.05,有统计学差异。结论 （1）大鼠肝脏组织存在Apelin表达。（2）Apelin可能参与了胰岛素抵抗的发生。     

肥胖及2型糖尿病患者血清apelin水平及其相关因素分析

目的测定肥胖及新诊断2型糖尿病患者血清apelin水平，探讨apelin与体脂、糖、脂代谢、胰岛素抵抗等的相关性。方法62例2型糖尿病患者和72例正常糖调节（NGR）者按体重指数（BMI）≥25kg／m^2或〈25kg／m^2又各自分为超重／肥胖与正常体重亚组，采用放射免疫分析法检测空腹血清apelin水平，同时检测空腹血糖（FPG）、HbA1C、血脂各项指标及空腹胰岛素（FINS）水平，计算BMI和腰臀比，并以稳态模型计算胰岛素抵抗指数（HOMA-IR）。结果校正年龄及性别后，2型糖尿病组血清apelin水平高于NGR组[（317．9±99．6vs279．0±66．8）ng／L，P〈0．01]，2型糖尿病组和NGR组中的超重／肥胖者均高于非肥胖者[（354．0±114．4vs274．1±53．0）ng／L，（299．2±74．5vs252．8±48．9）ng／L，均P〈0．05]，且2型糖尿病超重／肥胖组明显高于NGR肥胖组（P〈0．01）；偏相关分析显示，空腹血清apelin与BMI、ln（HOMA-IR）、FPG、总胆固醇（TC）呈正相关（r=0．353，r=0．355，r=0．224，r=0．241，均P〈0．01），与腰围、收缩压呈正相关（r=0．263，r=0．183，P〈0．05）。多元逐步回归分析发现，BMI、ln（HOMA—IR）和TC是血清apelin的独立相关因素。结论血清apelin水平在肥胖和初发的2型糖尿病人群中升高，且与BMI、HOMA-IR及脂代谢相关，推测apelin可能参与构成胰岛素抵抗综合征的病理生理基础。     

不同糖耐量人群血浆Apelin水平及其相关因素研究

比较了不同糖耐量人群血浆Apelin水平及其与BMI、血糖、胰岛素、血脂等的关系。发现IGT患者空腹和葡萄糖负荷后2h血浆Apelin水平明显高于正常对照组,血浆Apelin水平与HO-MA-IR、BMI、TC、LDL-C、FPG、FIns水平呈明显正相关。     

原发性高血压合并冠心病患者血清Apelin水平及其意义

目的观察原发性高血压（EH）合并冠心病（CHD）患者血清Apelin水平,并探讨其在冠心病中的意义。方法选择2013年6月至2013年12月原发性高血压患者96例作为观察对象,根据有无合并冠心病分为原发性高血压并冠心病组（EH并CHD组）53例、原发性高血压组（EH组）43例。检测两组血清Apelin水平、生物化学指标,计算体质指数,EH并CHD组行冠状动脉造影,计算Syntax评分,并进行统计学分析。结果（1）EH并CHD组血清Apelin水平明显低于EH组（1.83±0.71μg/L比2.28±0.82μg/L,P<0.05）。（2）随着Syntax评分增高,Apelin水平越低。（3）经Pearson相关分析,EH并CHD组血清Apelin与体质指数、收缩压、舒张压、空腹血糖呈负相关。（4）Logistic回归分析显示：血清Apelin降低是高血压患者发生冠心病的一个独立危险因素（OR＝0.475,95%CI：0.163～0.838,P<0.05）。结论与原发性高血压患者相比,原发性高血压合并冠心病患者血清Apelin水平进一步降低,提示血清Apelin水平测定可预测原发性高血压患者合并冠心病的风险。     

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0?ppm ozone for 4?h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.     

高血压病患者血浆Apelin-12和踝臂指数的相关影响因素

目的探讨高血压病（EH）患者血浆Apelin-12浓度和踝臂指数（ABI）的影响因素。方法EH患者45名，酶免疫法测定血浆Apelin-12浓度、并测定ABI、体重指数（BMI）、血糖、血脂、平均动脉压（MAP）等，30名健康志愿者作对照组。以Apelin-12和ABI为应变量，进行多元线性回归统计分析。结果（1）EH患者血浆Apelin-12浓度低于健康对照组（P=0．000）。（2）EH患者中Apelin-12浓度与BMI呈正相关（B=0．071，P=0．001），与平均动脉压呈负相关（B=0．016，P=0．020）。（3）EH患者中ABI值与年龄（B=-0．0045，P=0．030）、EH病程（B=-0．0069，P=0．020）、低密度脂蛋白浓度（LDL-C，B=-0．0562，P=0．024）负相关，与高密度脂蛋白浓度（HDL-C）呈正相关（B=0．268，P=0．002）。（4）EH患者中，Apelin-12与ABI间相关性并不显著（B=0．0697，P=0．096）。结论（1）血浆Apelin浓度下降可能是EH的发病机制之一。（2）EH患者中BMI和平均动脉压是Apelin-12浓度最重要的影响因素。