慢性缺氧性肺动脉高压大鼠右心室apelin-APJ基因表达降低

目的:研究慢性缺氧性肺动脉高压大鼠右心室组织apelin及其受体(APJ)基因表达的变化,探讨其在该病理过程中可能的作用及意义。方法:清洁级雄性SD大鼠20只,随机分为对照组和慢性缺氧组(10%O2,4w)。RT-PCR检测大鼠右心室apelin、APJ mRNA的表达变化。结果:①慢性缺氧组大鼠平均肺动脉压、右心室与左心室加室间隔重量比(RV/LV S)均显著高于对照组(P<0.01);②慢性缺氧组大鼠右心室apelin和APJ的mRNA表达均显著低于对照组(P<0.01)。结论:慢性缺氧性肺动脉高压大鼠右心室apelin-APJ系统表达降低,提示这一信号转导通路可能在慢性缺氧性肺动脉高压的发生发展中具有重要作用。     

APJ receptor mRNA expression in the rat hypothalamic paraventricular nucleus: regulation by stress and glucocorticoids

The apelin receptor (APJ receptor, APJR) has recently come to prominence following the isolation and identification of its endogenous ligand, apelin, from bovine stomach tissue extracts. Investigation of APJR mRNA expression has revealed a hypothalamic distribution similar to that of vasopressin suggesting that the apelin-APJR system may be involved in the regulation of the hypothalamic-adrenal-pituitary (HPA) stress axis. To investigate whether APJR is involved in the regulation of hypothalamic function during stress, APJR mRNA expression levels were measured by in situ hybridization in the hypothalamus of rats subjected to acute and repeated restraint stress. Acute stress caused an increase in APJR mRNA expression in the hypothalamic parvocellular paraventricular nucleus (pPVN) while repeated restraint stress induced a sustained up-regulation of pPVN APJR mRNA expression in intact rats. Removal of endogenous glucocorticoids by adrenalectomy also resulted in an increased expression of APJR mRNA in the PVN, suggesting a negative regulation of APJR mRNA expression by glucocorticoids. The role of glucocorticoids in mediating these stress-induced changes was investigated by analysing the effects of acute and repeated restraint stress on APJR mRNA levels in adrenalectomized rats. In these rats, APJR mRNA expression levels did not change above the already elevated levels of adrenalectomized-control rats. These data suggest that acute and repeated stress exert a stimulatory influence on APJR mRNA expression at the hypothalamic level that may be dependent on basal levels of circulating glucocorticoids, and further suggest a role for APJR in the regulation of hypothalamic function.     

Apelin/APJ系统与冠心病研究进展

Apelin是最近发现的一种血管内皮源性肽,而APJ(又命名为AGTRL1,血管紧张素Ⅱ1型受体相关受体)是它的内源性配体。Apelin/APJ系统广泛分布于机体的心血管以及神经内分泌等系统,并与肥胖、糖尿病及其并发症具有明显的相关性。最近关于Apelin/APJ系统与冠心病的关系研究较多,众多的研究结果显示Apelin/APJ系统与冠心病心绞痛及心肌梗死等皆存在明显的相关性。     

The relationship between serum apelin levels and aortic dilatation in bicuspid aortic valve patients

Objective: The bicuspid aortic valve (BAV) is the most common congenital heart dis‐ease. The process of aortic dilatation is not completely clear in patients with the BAV. Apelin is a peptide found at high levels in vascular endothelial cells which has a role in vascular regulation and cardiovascular function. The aim of this study was to de‐termine the relationship between serum apelin levels and ascending aortic dilatation in adult patients with BAV.
Design: This cross‐sectional study included 62 patients with isolated BAV and to an age, gender, and body mass index‐matched control group of 58 healthy volunteers with tricuspid aortic valve. Transesophageal echocardiography was performed on all patients to determine the type of BAV. Aortic diameters of the aortic root, sinus val‐salva, sinotubular junction, and ascending aorta were evaluated with echocardiogra‐phy. Patients with BAV were divided into two subgroups according to the aortic diameters, as the nondilated BAV group and the dilated BAV group. Serum apelin level was analyzed with ELISA method.
Results: The serum apelin levels of the BAV patients were significantly lower than those of the control group (833.5, 25th‐75th percentile (713.5‐1745) pg/dL vs 1669 (936‐2543) pg/dL; P = 0.006). In the subgroup analysis, serum apelin level was signifi‐cantly different between the nondilated BAV group and the dilated BAV group [977 (790‐2433) pg/dL vs 737 (693‐870) pg/dL, P < 0.05] and between the dilated BAV group and the control group [737 (693‐870) pg/dL vs 1669 (936‐2543) pg/dL, P < 0.001]. In multivariate logistic regression analysis apelin [7.27 (95% CI: 1.73‐30.42), P = 0.007] and age [1.05 (95% CI: 0.99‐1.20), P = 0.049] were determined as inde‐pendent predictors for ascending aortic dilatation.
Conclusion: Low serum apelin level was associated with dilatation of ascending aor‐tic in BAV patients. However, apelin was not relevant to BAV without aortic dilatation.     

罗格列酮与二甲双胍对新诊断2型糖尿病患者血清apelin及内脂素水平的影响

目的探讨罗格列酮和二甲双胍对新诊2型糖尿病患者血清apelin和内脂素水平的影响。方法初诊2型糖尿病患者100例,随机分为两组各50例,分别用罗格列酮和二甲双胍治疗,疗程12周。比较治疗前后两组空腹血糖（FPG）、空腹胰岛素（FINS）、糖化血红蛋白（HbA1 c）、内脂素、apelin、超敏C反应蛋白（hs-CRP）等指标的变化。结果治疗后两组apelin明显升高、罗格列酮组内脂素明显下降（P均〈0.05）。apelin与HbA1 c、HOMA-IR呈负相关（r分别为-0.22、-0.28,P均〈0.05）,内脂素与HbA1 c、hs-CRP、HOMA-IR呈正相关（r分别为0.26、0.41、0.33,P均〈0.05）。结论罗格列酮和二甲双胍均可影响新诊断2型糖尿病患者的血清apelin及内脂素水平。     

葛根素对两肾一夹高血压大鼠apelin及其受体的影响

目的:探讨葛根素对两肾一夹高血压大鼠apelin及其受体变化的影响.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)以及左心重与体重比值(LVM/BW)来评价高血压模型.放免法测定血浆、左心室组织匀浆apelin水平,免疫组化和RT-PCR分别检测左心室组织apelin,APJ表达的变化.结果: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),20.24%(P＜0.01).与模型组相比,葛根素组大鼠LVEDP,LVM/BW分别降低65.24%(P＜0.05),13.12%(P＜0.05),2组大鼠mCAP差异无统计学意义.放免结果:模型组血浆和左心室匀浆apelin-36浓度较正常组高18.56%(P＜0.05),207.38%(P＜0.05),而葛根素组较模型组降低24.21%(P＜0.05),49.40%(P＜0.05).RT-PCR结果:左心室组织apelin mRNA,APJ mRNA表达水平,模型组比正常组分别高77.66%(P＜0.05),119.00%(P＜0.05);而葛根素组较模型组降低27.40%(P＜0.01),45.66%(P＜0.01).免疫组化染色结果:左心室组织apelin和APJ蛋白表达水平,模型组较正常组分别高129.51%,154.1%(P＜0.01);而葛根素组较模型组降低65.36%(P＜0.01),62.87%(P＜0.01).结论:葛根素对肾陛高血压左室肥厚具有保护作用,该作用可能是通过调节apelin及其受体表达实现的.     

The apelinergic system: a promising therapeutic target

Importance of the field: Apelin is a bioactive peptide known as the ligand of the G-protein-coupled receptor APJ. In recent years, there has been a growing body of evidence regarding the importance of apelin and APJ in the pathophysiology of cardiovascular, metabolic and gastrointestinal diseases, brain signalling, HIV infection and tumor angiogenesis. Therefore, the apelinergic system is involved in the pathogenesis of several diseases that represent a major burden to our society.

Areas covered in this review: The goal of this paper is to give an up-to-date review of existing information on apelin/APJ since the discovery of apelin in 1998, with particular focus on their involvement in the regulation of human body systems and potential therapeutic applications.

What the reader will gain: An overview of the most important physiological functions of the apelinergic system and the diseases that may benefit in the future from its modulation as a therapeutic target.

Take home message: Today, the established biological effects of apelin involve major cardiovascular actions, neoangiogenesis, immunologic modulation and insulinemia control as well as body fluid and glucose homeostasis. However, the physiological and pathophysiological role of endogenous apelin is still unsettled and a better and profound knowledge of this system in humans is necessary for the development of novel apelinergic-based therapeutic targets.     

apelin-APJ系统基因单核苷酸多态性与糖尿病视网膜病变的关系

目的　研究apelin-APJ系统基因单核苷酸多态性（single nucleotide polymorphism,SNP）与糖尿病视网膜病变（diabetic retinopathy,DR）的关系。方法　横断面研究。自2017年7月至2018年7月纳入2型糖尿病患者885例,参照DR国际临床分型标准对患者进行分组,其中DR组346例,非DR（non-DR,NDR）组539例。两组均行眼部检查,计算体质量指数,测量血压,检测空腹血糖,并进行血液生化指标及血脂等实验室检查。采用定量PCR方法获得apelin基因rs3115757、rs56204867、rs3761581和APJ基因rs7119375、rs9943582共5个位点的基因分型,比较不同性别两组间各基因型分布的差异,采用Logistic回归分析apelin和APJ基因5个SNP与DR的关系。结果　无论男性还是女性,DR组糖尿病病程均显著长于NDR组（均为P=0.000）。男性apelin基因的3个SNP位点突变等位基因频率在DR组与NDR组间分布差异均有统计学意义（均为P<0.05）,APJ基因2个SNP突变位点等位基因频率在DR组与NDR组间分布差异均无统计学意义（均为P>0.05）。女性的5个SNP突变位点等位基因频率在DR组与NDR组间分布差异均无统计学意义（均为P>0.05）。调整年龄、体质量指数、空腹血糖后,Logistic回归分析结果显示,无论男性还是女性,携带rs3115757-C、rs56204867-C、rs3761581-A突变等位基因者患DR的风险均明显高于携带相应野生等位基因者（均为P<0.05）。结论　apelin基因的3个SNP rs3115757、rs56204867、rs3761581与DR的发生有关。     

Serum apelin is associated with affective disorders in peritoneal dialysis patients

Objective: Depression and anxiety are prevalent affective disorders in peritoneal dialysis (PD) patients. Recent research has proposed a potential role of apelinergic system in pathogenesis of depression. The present study aimed to evaluate the frequency of depression and anxiety and their potential relation with serum apelin levels among PD patients.

Methods: A total of 40 PD patients were enrolled into the study. Depressive symptoms and anxiety were assessed with the Beck’s Depression Inventory and the Beck’s Anxiety Inventory. Serum apelin-12 levels were measured by immunoenzymatic assays using commercially available ELISA kit for standard human apelin.

Results: Of the patients, 16 (40%) had depression, 20 (50%) had anxiety. The patients with depression and anxiety had a significantly longer time on dialysis (p?<?0.001 for both), significantly higher serum apelin (p?<?0.001 for both) and C-reactive protein levels (p?<?0.001 for both) than those without depression and anxiety. In multivariate analysis, serum apelin was the only parameter associated independently with depression and anxiety scores.

Conclusions: A substantial number of PD patients had depression and anxiety. Increased levels of serum apelin may constitute a significant independent predictor of development of depression and anxiety in PD patients.