急性心力衰竭患者血清Adropin、sST2、Gal-3水平与预后的关系分析

目的:探讨急性心力衰竭患者血清Adropin、可溶性ST2受体(s ST2)、半乳糖凝集素-3(Gal-3)水平与预后的关系。方法:选取2015年6月～2019年6月期间内蒙古自治区人民医院收治的154例急性心力衰竭患者纳入心衰组,另选同期在内蒙古自治区人民医院进行健康体检的100例志愿者为对照组。对比心衰组、对照组血清Adropin、s ST2、Gal-3水平,并将心衰组患者按美国纽约心脏病协会(NYHA)心功能分级分为II级组(n=38)、III级组(n=64)、IV级组(n=52),对比三组患者的血清Adropin、s ST2、Gal-3水平。心衰组患者经治疗出院后,根据患者的预后效果分为预后良好组(n=95)和预后不良组(n=59),采用单因素和Logistic多元回归分析急性心力衰竭患者预后不良的影响因素。结果:心衰组血清Adropin、s ST2、Gal-3水平均高于对照组(P0.05)。心衰组患者中随着心功能分级的升高,患者的血清Adropin、s ST2、Gal-3水平均显著升高(P0.05)。预后不良患者59例,发生率为38.31%。单因素分析结果显示,预后不良组和预后良好组患者在年龄、性别、体质指数(BMI)、吸烟史、饮酒史、基础疾病、血常规指标的比较无统计学差异(P0.05)。预后不良组患者的心功能分级、血清Adropin、s ST2、Gal-3水平均高于预后良好组(P0.05)。Logistic多元回归分析显示,心功能分级为IV级、Adropin≥10ng/mL、s ST2≥150μg/m L、Gal-3≥5μg/L是急性心力衰竭患者预后不良的危险因素(P0.05)。结论:急性心力衰竭患者血清Adropin、s ST2、Gal-3水平显著升高,并随患者的病情加重而升高,血清Adropin、s ST2、Gal-3水平的变化会影响患者的预后。     

Neuroprotective effect of ischemic preconditioning via modulating the expression of adropin and oxidative markers against transient cerebral ischemia in diabetic rats

IntroductionIschemic preconditioning (IPreC) can render the brain more tolerant to a subsequent potential lethal ischemic injury. Hyperglycemia has been shown to increase the size of ischemic stroke and worsen the clinical outcome following a stroke, thus exacerbating oxidative stress. Adropin has a significant association with cardiovascular disease, especially with diabetes. In this study, we aimed to evaluate the role of the IPreC due to modulating the expression of adropin and oxidative damage markers against stroke by induced transient middle cerebral artery occlusion (MCAo) in streptozotocin (STZ)-induced diabetic rats.Material-method72 male Spraque Dawley rats were allocated to 8 groups. In order to evaluate alterations of anti/oxidative status and adropin level, we induced transient MCAo seven days after STZ-induced diabetes. Also we performed IPreC 72 h before transient MCAo to assess whether IPreC could have a neuroprotective effect against ischemia-reperfusion injury.ResultsThe general characteristics of STZ-treated rats (STZ) included reduced body weight and elevated blood glucose levels compared to non-diabetic ones. Ischemic preconditioning before cerebral ischemia significantly reduced infarction size compared with the other groups [IPreC + MCAo (27 ± 11 mm³) vs. MCAo (109 ± 17 mm³) p < 0.001; STZ + IPreC + MCAo (38 ± 10 mm³) vs. STZ + MCAo (165 ± 45 mm³) p < 0.001, respectively]. The mean total antioxidant status level in IPreC groups was higher than other groups (p ≤ 0.05). Moreover, IPreC considerably decreased mean adropin levels compared with other groups (p ≤ 0.05).ConclusionThe study results supported the neuroprotective effects of ischemic preconditioning in MCA infarcts correlated with the level of oxidative damage markers and adropin.     

Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia-like conditions

Adropin is a peptide encoded by the energy homeostasis associated gene (Enho) and plays a critical role in the regulation of lipid metabolism, insulin sensitivity, and endothelial function. Little is known of the effects of adropin in the brain and whether this peptide modulates ischemia-induced blood-brain barrier (BBB) injury. Here, we used an in vitro BBB model of rat brain microvascular endothelial cells (RBE4) and hypothesized that adropin would reduce endothelial permeability during ischemic conditions. To mimic ischemic conditions in vitro, RBE4 cell monolayers were subjected to 16 h hypoxia/low glucose (HLG). This resulted in a significant increase in paracellular permeability to FITC-labeled dextran (40 kDa), a dramatic upregulation of vascular endothelial growth factor (VEGF), and the loss of junction proteins occludin and VE-cadherin. Notably, HLG also significantly decreased Enho expression and adropin levels. Treatment of RBE4 cells with synthetic adropin (1, 10 and 100 ng/ml) concentration-dependently reduced endothelial permeability after HLG, but this was not mediated through protection to junction proteins or through reduced levels of VEGF. We found that HLG dramatically increased myosin light chain 2 (MLC2) phosphorylation in RBE4 cells, which was significantly reduced by adropin treatment. We also found that HLG significantly increased Rho-associated kinase (ROCK) activity, a critical upstream effector of MLC2 phosphorylation, and that adropin treatment attenuated that effect. These data indicate that treatment with adropin reduces endothelial cell permeability after HLG insult by inhibition of the ROCK-MLC2 signaling pathway. These promising findings suggest that adropin protects against endothelial barrier dysfunction during ischemic conditions.     

Three new players in energy regulation: Preptin,adropin and irisin

Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.     

远端血管通路导管治疗急性脑梗死对血清Adropin蛋白、载脂蛋白A1的影响

摘要 目的：探讨远端血管通路导管治疗急性脑梗死对血清Adropin蛋白、载脂蛋白A1（ApoA1）的影响。方法：将2018年6月到2021年4月选择在本院急诊的急性脑梗死患者84例作为研究对象,根据随机信封1:1抽签原则把患者分为导管组与支架组,各42例。支架组给予支架溶栓治疗,导管组给予远端血管通路导管治疗,比较两组手术相关指标、mTICI分级情况、脑血液流变学变化以及血清Adropin、ApoA1含量等指标。结果：导管组的导引导管到位时间、血管获得再通时间均较支架组少（P<0.05）;导管组治疗后1个月的血管灌注改良脑梗死溶栓试验（mTICI）分级优于支架组（P<0.05）;两组颅脑椎动脉与基底动脉血流速度治疗前均无差异（P>0.05）,治疗后两组的颅脑椎动脉与基底动脉血流速度高于治疗前（P<0.05）,导管组较支架组高（P<0.05）;两组血清Adropin、ApoA1含量治疗前对比无差异（P>0.05）,治疗后两组的血清Adropin、ApoA1含量较治疗前高（P<0.05）,导管组较支架组高（P<0.05）。结论：远端血管通路导管治疗急性脑梗死可加快手术操作改善患者的血管灌注分级情况,促进血清Adropin、ApoA1的释放,有利于患者脑动脉血流速度的恢复。     

Adropin Is a Brain Membrane-bound Protein Regulating Physical Activity via the NB-3/Notch Signaling Pathway in Mice

Adropin is a highly conserved polypeptide that has been suggested to act as an endocrine factor that plays important roles in metabolic regulation, insulin sensitivity, and endothelial functions. However, in this study, we provide evidence demonstrating that adropin is a plasma membrane protein expressed abundantly in the brain. Using a yeast two-hybrid screening approach, we identified NB-3/Contactin 6, a brain-specific, non-canonical, membrane-tethered Notch1 ligand, as an interaction partner of adropin. Furthermore, this interaction promotes NB3-induced activation of Notch signaling and the expression of Notch target genes. We also generated and characterized adropin knockout mice to explore the role of adropin in vivo. Adropin knockout mice exhibited decreased locomotor activity and impaired motor coordination coupled with defective synapse formation, a phenotype similar to NB-3 knockout mice. Taken together, our data suggest that adropin is a membrane-bound protein that interacts with the brain-specific Notch1 ligand NB3. It regulates physical activity and motor coordination via the NB-3/Notch signaling pathway and plays an important role in cerebellum development in mice.     

Tilapia adropin: the localization and regulation of growth hormone gene expression in pituitary cells

The peptide hormone adropin, encoded by the energy homeostasis-associated (Enho) gene, plays a role in energy homeostasis and the control of vascular function. The aim of this study was to examine the role of adropin in growth hormone (GH) gene expression at the pituitary level in tilapia. As a first step, the antiserum for the tilapia adropin was produced, and its specificity was confirmed by antiserum preabsorption and immunohistochemical staining in the tilapia pituitary. Adropin could be detected immunocytochemically in the proximal pars distalis (PPD) of the tilapia pituitary. In primary cultures of tilapia pituitary cells, tilapia adropin was effective in increasing GH mRNA levels. However, removal of endogenous adropin by immunoneutralization using adropin antiserum inhibited GH gene expression. In parallel experiments, pituitary cells co-treated with ovine pituitary adenylate cyclase activating polypeptide 38 (oPACAP38) and adropin showed a similar increase level compared to those treated with oPACAP38 alone, whereas insulin-like growth factor 1 (IGF1) not only had an inhibitory effect on basal GH mRNA levels, but also could abolish adropin stimulation of GH gene expression. In pituitary cells pretreated with actinomycin D, the half-life of GH mRNA was enhanced by adropin. Taken together, these findings suggest that adropin may serve as a novel local stimulator for GH gene expression in tilapia pituitary.     

Copeptin,adropin and irisin concentrations in breast milk and plasma of healthy women and those with gestational diabetes mellitus

Copeptin, adropin and irisin are polypeptide hormones implicated in energy homostasis and diabetes. The purposes of this study were (1) to compare the copeptin, adropin and irisin concentrations between colostrum, transitional and mature milk and plasma in lactating women with and without GDM and (2) to compare these values with those from non-lactating women. Venous blood samples were obtained before suckling from 15 healthy lactating women aged 26–30 years, 15 lactating women with GDM aged 26–32 years, and 14 age-matched controls aged 25–31 years. Colostrum, transitional milk and mature milk samples were collected just before suckling. The concentration of copeptin was determined by EIA while the concentrations of adropin and irisin were determined by ELISA. The levels of copeptin, adropin and irisin in the colostrum were significantly higher than those in transitional and mature milk samples from healthy women; also, transitional milk had higher copeptin, adropin and irisin concentrations than mature milk. The amounts of copeptin in the colostrum and transitional milk were significantly higher than in mature milk samples from women with GDM, while the amounts of adropin and irisin were significantly lower. The relative concentrations of copeptin, adropin and irisin in the plasma samples from these groups of women were similar to those in the colostrum, transitional and mature milk samples, but the latter concentrations were higher than those in the plasma. These peptides could influence the regulation of metabolic pathways and the postnatal growth and development of different organs in the newborn.