大鼠心肌APJ受体及caveolin-1/ERK1/2表达的年龄变化研究

目的apelin是新发现的内源性肽,其受体是G蛋白偶联受体APJ,该实验比较不同年龄大鼠心肌APJ受体及信号分子caveolin-1/ERK1/2的表达差异。方法采用West-ern blot方法观察胎鼠、乳鼠、成年鼠、老龄鼠等不同年龄阶段心肌组织APJ受体、ERK1/2、pERK1/2、caveolin-1的表达及其增龄性变化。结果随年龄增长APJ受体、caveolin-1表达增加,ERK1/2及pERK1/2随年龄增长表达减少。结论APJ受体及其caveolin-1/ERK1/2途径可能与心脏的生长发育、衰老过程有关。     

葛根素对两肾一夹高血压大鼠左心室Apelin／APJ基因表达的影响

目的:探讨葛根素对两肾一夹(2K1C)高血压大鼠左心室Apelin/Apj基因表达的影响。方法:清洁级雄性SD大鼠30只,随机均分为正常组、模型组和葛根素组。分别测定平均颈动脉压(mCAP)、左室舒张末期压(LVEDP)以及左心室压力变化最大速率(LV±dp/dtmax),左心重与体重比值(LVM/BW)来评价高血压模型。RT-PCR方法检测左心室组织apelin、APJ基因表达的变化。结果:①与正常组相比,模型组大鼠mCAP、LVEDP以及LVM/BW分别升高36.58%(P<0.05)、333.8%(P<0.01)和20.24%(P<0.01),而LV dp/dtmax则降低85.35%(P<0.05)。两组大鼠LV-dp/dtmax差异无统计学意义。②与模型组相比,葛根素组大鼠LVEDP、LVM/BW以及LV-dp/dtmax分别降低65.24%(P<0.05)、13.12%(P<0.05)和96.28%(P<0.01),LV dp/dtmax则升高179.18%(P<0.01)。两组大鼠mCAP差异无统计学意义。③左心室组织apelinmRNA、APJmRNA表达水平:模型组比对照组分别高77.66%和119.00%(均P<0.05),而葛根素组较模型组分别低27.40%和45.66%(均P<0.05)。结论:Apelin/APJ系统可能在葛根素逆转大鼠左室肥厚的发生发展过程中扮演重要的角色。     

The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential

Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor, APJ. This novel peptidic signalling pathway is widely represented in the heart and vasculature, and is emerging as an important regulator of cardiovascular homeostasis. In preclinical models, apelin causes nitric oxide-dependent vasodilatation, reduces ventricular preload and afterload, and increases cardiac contractility in rats with normal and failing hearts. Apelin-APJ signalling also attenuates ischemic myocardial injury and maintains cardiac performance in ageing and chronic pressure overload. Downregulation of apelin and APJ expression coincides with declining cardiac performance raising the possibility that diminished apelin-APJ activity may have pathophysiologic implications. At present, data from human studies is limited but changes in apelin and APJ expression in patients with chronic heart failure parallel those seen in preclinical models. Detailed clinical investigation is now required to establish the role of apelin in human cardiovascular physiology and pathophysiology, and to determine the therapeutic potential of augmenting apelin signalling in patients with heart failure.     

心血管活性肽Apelin生物学功能研究进展

G蛋白偶联受体是指一大类与G蛋白偶联并参与和介导细胞外信号传递的跨膜蛋白,信号传导过程中与受体偶联的物质称为配体,对于不清楚内源性配体物质的G蛋白偶联受体称为孤儿G蛋白偶联受体。血管紧张素受体样受体是一种孤儿G蛋白偶联受体。其内源性配体Apelin新近从牛胃抽提液中被分离出来,现发现apelin的功能涉及心血管系统,中枢神经系统,免疫系统等。Apelin在血管紧张素Ⅰ转化酶的同源酶血管紧张素Ⅰ转化酶2的作用下有活性形式转变成无活性的形式。现对apelin在心血管系统以及以其它众多生物学功能研究进展作一综述。     

Apelin对人成骨细胞的作用

目的 研究apelin及其受体APJ在人成骨细胞的表达和apelin对成骨细胞的作用。方法 RT-PCR和Western印迹法检测apelin和APJ在人成骨细胞的表达。用apelin处理人成骨细胞，^3H掺入法（^3H-TdR）和细胞计数法测定细胞的增殖，通过测定细胞内碱性磷酸酶（ALP）活性、骨钙素分泌水平和Ⅰ型胶原的生成来分析细胞功能。Western印迹法检测信号通路的激活。通过小分子干扰核糖核酸（siRNA）技术阻断APJ，观察其对细胞增殖和信号通路的影响。结果Apelin和APJ在人成骨细胞均有表达，Apelin能促进人成骨细胞增殖，但对其ALP活性、骨钙素的分泌和Ⅰ型胶原的生成无影响。通过siRNA技术阻断APJ能消除apelin对细胞增殖的促进作用。Apelin能诱导人成骨细胞磷脂酰肌醇3激酶（P13K）下游底物蛋白激酶B（Akt）的活化，但不能诱导c-junN一端激酶（JNK）、p38和细胞外信号调节激酶1／2（ERK1／2）等丝裂原活化蛋白激酶（MAPK）的活化。siRNA干扰APJ对Akt的活化起抑制作用。P13K抑制剂（LY294002）能消除apelin对细胞增殖的促进作用和Akt的活化。结论 人成骨细胞表达apelin和APJ，Apelin通过APJ／P13K／Akt途径促进人成骨细胞增殖，但对其分化无影响。     

Apelin/APJ在PCOS模型大鼠卵巢中的表达及意义

目的:探讨Apelin/APJ在多囊卵巢综合征(PCOS)模型大鼠卵巢组织中的表达。方法:21日龄SD大鼠肌肉注射脱氢表雄酮(DHEA),建立PCOS大鼠模型(实验组,n=15),并以等量溶剂油代替DHEA为对照组(n=15),观察卵巢相对重量;HE染色观察卵巢改变;测定E2、T、P、FSH、LH水平;采用免疫组织化学法观察Apelin/APJ在PCOS卵巢中的分布与表达;荧光定量RT-PCR(quantitative RT-PCR)检测Apelin/APJ mRNA表达,Western-blotting检测Apelin/APJ蛋白表达。结果:apelin/APJ分别表达于大鼠卵泡膜细胞、颗粒细胞;实验组卵泡内膜、颗粒细胞中Apelin/APJ mRNA及蛋白表达均高于对照组(P<0.05)。结论:apelin/APJ的异常表达可能与PCOS复杂的发病有关。     

Targeting the elabela/apelin-apelin receptor axis as a novel therapeutic approach for hypertension

Hypertension is the leading risk factor for global mortality and morbidity and those with hypertension are more likely to develop severe symptoms in cardiovascular and cerebrovascular system, which is closely related to abnormal renin-angiotensin system and elabela/apelin-apelin receptor (APJ) axis. The elabela/apelin-APJ axis exerts essential roles in regulating blood pressure levels, vascular tone, and cardiovascular dysfunction in hypertension by counterbalancing the action of the angiotensin...     

ELA-Apelin-APJ系统在血管重构稳态与血管疾病中的调控作用及相关药物研发进展

Apelin受体（Apelin receptor,APJ）是一种G蛋白偶联受体,其内源性配体包括Elabela （ELA）和Apelin,在血管重构稳态和损伤修复中发挥重要作用。ELA-Apelin-APJ系统参与血管的生成、分化及纤维化,以及细胞凋亡、炎症反应、氧化应激及血压调控,其活性和表达异常参与动脉粥样硬化、高血压、肺动脉高压、脑卒中等血管疾病的发病过程。概述ELA-Apelin-APJ系统在血管重构稳态中的调控作用及其作为潜在药物靶点的研究新进展,以期为血管研究提供参考。     

Effects of Apelin-13/putative receptor protein related to AT1 homodimer on behaviors of human umbilical vein endothelial cells北大核心CSCD

Aim To explore the effects of putative receptor protein related to ATI (APJ) homodimer on the behaviors-the proliferation, migration and tube formation of human umbilical vein endothelial cells (HU-VECs). Methods HUVECs at logarithmic growth stage were randomly divided into PBS, Apelin-13 + TM1 (APJ monomer group) and Apelin-13 + PBS group (APJ homodimer group). Western blot and Matrix-Assisted Laser Desorption/Ionization Time of Fligh Mass Spectrometry (MALDI-TOF MS) were used to detect the expression of APJ and APJ homodimer in HUVECs, respectively. Real-Time Cell Analyzers (RT-CA) was used to detect the concentration of the maximum effect of Apelin-13. Cell viability was detected by CCK-8. The cell migration ability was detected by scratch test, and the number of tubes formed on matri-gel that made artificial basement membrane was counted. Results Western blot and MALDI-TOF MS showed that APJ and APJ homodimer were expressed in HUVECs. The EC50 of Apelin-13 was 2.26 x 10 -8 mol • L, and the concentration of the maximum effect was 1.0 X 10 mol • L. The results of CCK-8 experiment, migration experiment and tube formation showed that cells in each group migrated to the scratch bare area gradually with the extension of time, and the tube formation of cells in each group was also observed under the microscope. Data statistics showed that the proliferation, migration and tube forming abilities of HUVECs in Apelin-13 + PBS and Apelin-13 + TM1 groups were significantly higher than those in PBS group, and the abilities of proliferation, migration and tube forming in Apelin-13 + PBS group were significantly better than those in Apelin-13 + TM1 group (P < 0.05). Conclusions APJ homodimer can promote the proliferation, migration and tube formation of HUVECs, and the effects are better than APJ monomer. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Apelin-13促进骨髓间充质干细胞增殖

目的 探讨apelin-13是否促进骨髓间充质干细胞增殖。 方法 分离和培养大鼠骨髓间充质干细胞,用不同浓度apelin-13（0.1 μmol/L、1.0 μmol/L和10.0 μmol/L）处理细胞24 h后,分别用流式细胞术和噻唑蓝比色法（MTT）,观察apelin-13对骨髓间充质干细胞增殖的影响。 结果 倒置显微镜下观察到apelin-13促进大鼠骨髓间充质干细胞增殖,流式细胞术检测结果表明,apelin-13刺激后处于S期和G2-M期的细胞数目显著增加,G0-G1期的细胞数目显著减少。进一步MTT结果表明,apelin-13处理后大鼠骨髓间充质干细胞增殖显著增加,并呈浓度依赖性。 结论 apelin-13能促进骨髓间充质干细胞增殖。