Venous dilator effect of apelin,an endogenous peptide ligand for the orphan APJ receptor,in conscious rats

Apelin is an endogenous depressor peptide for the G protein-coupled APJ receptor. Our hypothesis is that apelin is a venodilator, and it reduces mean circulatory filling pressure (MCFP; index of venous tone). Dose–response curves of apelin (10, 20 and 40 nmol/kg) or vehicle (0.9% NaCl) were constructed in two groups each of conscious, unrestrained rats: unblocked rats and rats pretreated with mecamylamine (Mec; ganglionic blocker) and noradrenaline (NA; to restore vascular tone). The vehicle had no effects in the unblocked or ganglionic-blocked rats. Apelin decreased mean arterial pressure (MAP) and increased heart rate (HR), but it did not alter mean circulatory filling pressure in the unblocked rats. In the ganglionic-blocked rats, apelin did not alter heart rate but decreased mean arterial pressure and mean circulatory filling pressure. These results show that apelin is an arterial and venous dilator in vivo. The depressor effect of apelin is accompanied by tachycardia which is abolished by ganglion blockade.     

妊娠期糖尿病患者血清Apelin水平的变化研究

目的 通过观察妊娠期糖尿病(GDM)患者Apelin水平的变化,探讨Apelin与GDM的关系.方法 2015年6月至12月在本院门诊做产前检查孕妇,按诊断标准分为GDM组(86例),对照组(健康孕妇组,90例).分别在做OGTT试验时及诊断为GDM患者饮食控制后,检测FBG、TC、TG、HDL-C、LDL-C、空腹胰岛素(FINS)、Apelin,计算出HOMA-IRI评价胰岛素抵抗的指标.结果 在做OGTT试验时,检测健康孕妇组的FBG、TG、LDL-C、FINS、HOMA-IRI、Apelin与GDM组比较差异有统计学意义(P＜0.05).GDM患者饮食控制后,FBG、FINS、HOMA-IRI、Apelin与对照组比较差异有统计学意义(P＜0.05).GDM组的TG、LDL-C与对照组比较差异无统计学意义(P＞0.05).结论 研究表明GDM患者存在高水平胰岛素抵抗,胰岛素抵抗可引起FBG、TG、LDL-C、FINS、HOMA-IRI、Apelin升高;而脂类代谢对Apelin水平升高无影响.胰岛素抵抗如何使GDM患者Apelin水平升高,可能是GDM发生的重要机制.     

Apelin attenuates streptozotocin-induced learning and memory impairment by modulating necroptosis signaling pathway

Apelin is a neuropeptide that plays an important role in neuronal protection. In this study, we investigated the effects of apelin intracerebroventricular administration on spatial learning and memory-related behaviors, and necroptosis signaling pathways in the hippocampus of streptozotocin (STZ) -injected rats. Apelin treatment was implemented following STZ-induced dementia for 15 days. After conducting a behavioral test (Morris Water Maze), the cellular and molecular aspects were examined to detect the apelin effect on the necroptosis signaling pathway. We demonstrated that STZ administration significantly slowed down the learning capability. However apelin treatment notably reversed this neuroinflammation induced behavioral impairment. Furthermore, molecular investigations showed that apelin treatment reduced the hippocampal RIP1, RIP3, and TNF-α level. Our results suggest that apelin treatment attenuates STZ-induced dementia. This effect may be mediated by inhibition of the necroptosis signaling pathway which seems to be associated with the ability of apelin to reduce central TNF-α level. This data provides evidence of the neuroprotective effect of apelin on STZ-induced learning and memory impairment and characterize some of the underlying mechanisms.     

Apelin促进小鼠成骨细胞MC3T3-E1的增殖

目的观察Apelin对小鼠成骨细胞MC3T3-E1增殖和分化的作用,探讨其可能的作用机制。方法 RT-PCR检测MC3T3-E1细胞APJ（Apelin受体）的表达、Western blot、ELISA、放射免疫法和[3H]TdR-掺入法检测MAPKs和Akt的激活,以及MC3T3-E1细胞的增殖和分化指标;用PI3-K抑制剂LY294002,AKT抑制剂HIMO和JNK抑制剂SP600125预处理以观察Apelin影响MC3T3-E1细胞增殖的信号转导机制。结果 MC3T3-E1细胞表达APJ;Apelin对MC3T3-E1细胞碱性磷酸酶（alkali phosphatase,ALP）活性、骨钙素（osteocalcin,OC）和Ⅰ型胶原（type Ⅰ collagen）的分泌及Runx2蛋白的表达无影响;Apelin促进MC3T3-E1细胞增殖;Apelin诱导JNK和PI3-K/AKT的磷酸化;PI3-K抑制剂LY294002,AKT抑制剂HIMO和JNK抑制剂SP600125均可以抑制Apelin对MC3T3-E1细胞的促增殖作用。结论 MC3T3-E1细胞表达APJ;Apelin通过JNK和PI3-K信号转导通路促进MC3T3-E1细胞增殖,但对其分化无影响。     

Apelin抑制小鼠成骨细胞MC3T3-E1凋亡

目的观察Apelin对小鼠成骨细胞MC3T3-E1凋亡的作用。方法 ELISA和吖啶橙/溴乙啶（AO/EB）染色法检测细胞凋亡,Western blot检测细胞Bcl-2和Bax表达以及cytochrome c的分泌,通过荧光素（AFC、AMC）标记的底物来检测活性。结果 Apelin抑制无血清饥饿诱导的MC3T3-E1细胞凋亡;Apelin抑制无血清饥饿诱导的cyto-chrome c的分泌和caspase-3、caspase-8c、aspase-9的活化;Apelin抑制地塞米松或肿瘤坏死因子-α（TNF-α）诱导的MC3T3-E1细胞凋亡。结论 Apelin可抑制成骨细胞凋亡。     

Lowered circulating apelin is significantly associated with an increased risk for hypertension: A meta-analysis

Background and Objective: Apelin is a bioactive peptide manifesting a potent vasodilatory property. In this meta-analysis, we aimed to investigate for the first time whether circulating apelin differed significantly between hypertensive patients and normotensive controls. Methods: Both PubMed and Embase were searched for eligible articles. Eligibility evaluation and data collection were done independently by two investigators. Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated under random-effects model by STATA. Results: Ten studies were synthesized finally, including 1610 patients and 1105 controls. Overall analysis revealed that circulating apelin was significantly lowered in patients than in controls (WMD = ?39.85 pg/mL, 95% CI: ?65.56 to ?14.15; P = 0.002), with significant heterogeneity (I² = 89.4%). By race, patients had lower circulating apelin than controls in Caucasian populations (WMD = ?79.82 pg/mL, 95% CI: ?105.80 to ?53.85; P < 0.001), without heterogeneity (I²=0.0%), while no significance was observed in Chinese and African-Americans. Further grouping studies by source of controls found a significant reduction in circulating apelin in studies with hospital-based controls (WMD = ?96.28 pg/mL, 95% CI: ?129.67 to ?62.88; P < 0.001) (I² = 49.4%), but not in studies with population-based controls. Conclusions: Via a meta-analysis of 10 studies and on 2715 subjects, our findings demonstrated that lowered circulating apelin was significantly associated with an increased risk for hypertension, especially in Caucasian populations.     

儿童先天性心脏病血清Apelin水平与肺动脉压关系的初步探讨

目的 初步探讨先天性心脏病患儿血清Apelin 水平与肺动脉压的关系.方法 手术治疗的先心病患儿126 例,检测患儿术前及术后第7 天的血清Apelin 水平.建立体外循环前检测并计算肺动脉收缩压/体循环收缩压(Pp/Ps)的比值,依据Pp/Ps 分组:无肺动脉高组压(PAH)组、轻度PAH 组、中度PAH 组和重度PAH 组;术后第7 天超声心动图估测肺动脉平均压(PAMP).结果 无PAH,以及轻、中、重度PAH 各组术前及术后的血清Apelin 水平依次降低,差异有统计学意义(PPr=-0.51,-0.54,P结论 先心病患儿并发肺动脉高压及其发展与血清Apelin 水平降低有关系,血清Apelin 对诊断先心病患儿是否并发肺动脉高压及其程度的意义值得深入研究.     

大鼠侧脑室注射Apelin-13对急性痛的调节作用及机制

目的探讨Apelin-13对大鼠急性痛的调制作用及可能机制。 方法简单随机抽样将50只大鼠分为生理盐水组、Apelin-13 0.05μg/g组、Apelin-13 0.1μg/g组、Apelin-13 0.5μg/g组及吗啡组(阳性对照组),每组10只,采用辐射热甩尾法连续监测60 min内大鼠痛阈的变化;同样采用简单随机抽样将40只大鼠分为生理盐水组、Apelin-13 0.5 μg/g组、酪蛋白激酶2(CK2)抑制剂四溴苯三唑(TBB)组及Apelin-13＋TBB组,每组10只,监测其痛阈的变化。Western Blot法检测海马内CK2表达量及N-甲基-D-天冬氨酸(NMDA)受体NR2B亚单位(P-NR2B S1480)磷酸化水平,研究Apelin－13对急性痛调制作用可能的机制。 结果Apelin-13可显著升高急性痛痛阈,0.5 μg/g组给药10 min时甩尾潜伏期变化率(TWL%)达峰值[(50.03±2.71)%],与生理盐水组比较差异有统计学意义(q＝18.054,P＝0.003),并且此效应呈剂量和时间依赖(F_Group＝47.729,P＝0.000;F_Time＝205.301,P＝0.000)。同时给予CK2抑制剂TBB10 min时TWL%降至(17.75±1.67)%,低于Apelin-13组,差异有统计学意义(q＝6.976,P＝0.005)。Western Blot结果显示TBB可明显减弱Apelin-13的作用,CK2α表达量、NR2B亚单位磷酸化水平均下降[(26.92±4.38)%,(39.90±7.40)%],与Apelin-13组[(41.60±6.65)%,(70.83±3.52)%]比较差异有统计学意义(q＝5.246,P＝0.010;q＝9.757,P＝0.010)。 结论Apelin-13可能通过CK2促进NMDA受体NR2B亚单位磷酸化,进而在热甩尾急性痛模型中起镇痛作用。     

Serum levels of apelin,salusin-alpha and salusin-beta in normal pregnancy and preeclampsia

Objective: The purpose of this study was to investigate the relationship between the serum apelin, salusin-alpha and salusin-beta levels and preeclampsia. Method: Twenty-one healthy pregnant women (control group) and 48 patients with preeclampsia (study group) were included in the study between August 2010 and February 2011. Serum apelin, salusin-alpha and salusin-beta levels of the groups were compared. Results: The patients in the study group were divided into two categories: mild preeclampsia and severe preeclampsia. The mild preeclampsia group consisted of 31 patients, and the severe preeclampsia group consisted of 17 patients. Serum salusin-alpha and salusin-beta levels of the control and study groups were not significantly different (p > 0.05). Apelin levels were statistically significantly higher in the study group. No statistically significant difference was detected between the mild and severe preeclampsia groups in terms of the mean serum apelin levels. Conclusion: The serum levels of apelin were higher in the pregnant women with preeclampsia; however, there was no positive relationship between serum salusin-alpha and salusin-beta levels and the disease. Larger prospective studies are needed to validate our findings.