视黄醇结合蛋白4遗传多态性与2型糖尿病的关系

视黄醇结合蛋白（retinol binding protein,RBP）属于视黄醇运载蛋白,其血清水平常作为临床营养状况、肝肾疾病的早期诊断和疗效的评价指标。最新研究发现：视黄醇结合蛋白4（RBP4）为一种新的脂肪源性信使,参与了胰岛素抵抗和2型糖尿病的发生。这一发现使得RBP4开始倍受关注。本文主要介绍视RBP4的结构、遗传多态性及其与2型糖尿病之间的最新研究进展。     

血清视黄醇结合蛋白4与冠心病的关系探讨及相关因素分析

<正>由脂肪细胞合成分泌的脂肪细胞因子影响糖脂代谢、胰岛素抵抗(IR)和向心型肥胖等[1],这些代谢异常都是心血管疾病的重要危险因素。视黄醇结合蛋白4(RBP4)是一种新的循环性脂肪源性因子,属于视黄醇结合蛋白(RBP)家族中的分泌型RBP,主要由肝细胞和脂肪细胞分泌,在协助视黄醇     

视黄醇结合蛋白测定及临床应用研究进展

视黄醇结合蛋白（Retinolblindingprotein,RBP）为血浆中的一种小分子蛋白质,是血中维生素A的特异转运蛋白,1968年由Kanai等首次分离,1971年Peterson和Beeggard从尿中将其分离。RBP具有从肝细胞中转运视黄醇至周围组织的功能,在体内维生素A的代谢中发挥重要作用,近年来,视黄醇结合蛋白检测及临床应用日益受到关注,检测血和尿中视黄醇结合蛋白,对肾脏、肝脏及营养状况等疾病的诊断和治疗有着重要意义。本文对视黄醇结合蛋白的理化特性、检测方法及临床应用进行阐述。     

尿微量白蛋白及视黄醇结合蛋白联合检测对糖尿病肾病的早期诊断

目的 探讨尿微量白蛋白（mALB）及视黄醇结合蛋白（RBP）联合检测在糖尿病肾病的早期诊断价值。方法对所有研究对象均留取晨尿5ml,离心取上清夜,检测mALB及RBP。结果糖尿病组尿微量白蛋白及视黄醇结合蛋白均显著显著高于对照组（P〈0．01）。结论联合检测尿mALB及RBP可提高糖尿病早期肾损害的检出及判断肾损害的部位。     

视黄醇结合蛋白4与妊娠期糖尿病的相关性研究

目的探讨血清视黄醇结合蛋白4（RBP4）与妊娠期糖尿病（GDM）的关系。方法选取产科门诊孕24～28周的孕妇,糖耐量正常组（NGT）40人、糖耐量减低组（GIGT）42人、妊娠期糖尿病组（GDM）38人,采用ELISA方法测空腹RBP4,并测空腹血糖（FPG）、空腹胰岛素（FINS）,计算胰岛素抵抗指数（HOMA-IR）,分析各指标间的相关性。结果血清RBP4浓度在NGT组、GIGT组、GDM组依次升高,差异有统计学意义（P〈0.01）。血清RBP4浓度与FPG、FINS、HOMA-IR呈显著正相关（P〈0.01）。结论 RBP4与GDM的发生有明显相关性,可能参与了GDM的胰岛素抵抗。     

血清视黄醇结合蛋白4与非酒精性脂肪肝病的相关性研究

目的分析血清视黄醇结合蛋白4（RBP4）在非酒精性脂肪肝病（NAFLD）患者中的水平,探讨血清RBP4与NAFLD的相关性。方法分别测定85例NAFLD患者和94例健康对照组的体重指数（BMI）、血压及生化指标,采用Pearson’s相关分析,研究RBP4与BMI、SP、DP、ALT、GGT、FBG、TG等检测因素的相关性。结果NAFLD组血清RBP4水平显著高于对照组[（64.6±15.1）mg/LVs（53.7±13.4）mg/L],P〈0.001）;采用Pearson’s单相关分析显示,血清RBP4水平与ALT、HOMA、GGT显著正相关（P〈0.01）,与GGT相关关系密切（r=0.486,P〈0.001）;多因素Logistic回归分析显示,血清RBP4是与NAFLD相关联的独立影响因子（P=0.004;OR（95%CI）：1.055（1.020-1.103））。结论血清RBP4水平与NAFLD及肝细胞凋亡和损伤标志物显著相关。     

血清视黄醇结合蛋白4和 Apelin-12与稳定性心绞痛患者冠状动脉狭窄的相关性研究

目的：检测稳定性心绞痛患者血清视黄醇结合蛋白4（ RBP4）和Apelin-12水平的变化,探讨其与冠状动脉狭窄程度、病变部位的关系。方法以酶联免疫吸附法测定血清视黄醇结合蛋白4和Apelin-12水平;依据冠状动脉造影检查和Gensini评分结果分组,将Gensini积分（GS）按照四分位数间距划分为四组：GS≤18,18～32,32～47,＞47。结果与对照组比较,RBP4在GS1及GS2组中均明显高于对照组,Apelin-12明显低于对照组（P＜0．001）。与对照组比较,RBP4在单支、双支、三支病变组中均高于对照组（P＜0．001）,单支、双支病变组之间差异无统计学意义（P＞0．05）,但在单支与三支病变组之间差异有统计学意义（P＜0．001）;Apelin-12在单支、双支及三支病变组之间差异均有统计学意义（P＜0．001）。与对照组比较,RBP4在LAD病变组中高于对照组、Apelin-12在LAD病变组中显著低于对照组,两者在RCA、LCX病变组与对照组之间差异无统计学意义（ P＞0．05）。结论血清RBP4、Apelin-12水平和稳定性心绞痛患者冠脉病变狭窄程度有关,并且与冠状动脉病变部位有关。     

血清视黄醇结合蛋白水平与肝硬化Child-Pugh分级的相关性分析

目的 探讨血清视黄醇结合蛋白(RBP)水平与肝硬化Child-Pugh分级的关系.方法 选取我院2012年1月1日～2013年12月31日住院的肝硬化患者93例,根据Child-Pugh分级分为A、B、C3组,对照组为正常健康人40例,应用酶联免疫吸附法检测各组的血清视黄醇结合蛋白(RBP)水平.结果 肝硬化患者视黄醇结合蛋白(RBP)计数明显高于正常对照组,差异有统计学意义(P＜0.05).且视黄醇结合蛋白(RBP)与肝硬化Child-Pugh分级呈负相关.结论 血清视黄醇结合蛋白(RBP)水平可作为评价肝硬化患者肝功能损害程度的一项敏感指标.     

视黄醇结合蛋白4早期评估冠状动脉粥样硬化的研究进展

视黄醇结合蛋白4(Retinol binding protein,RBP4)是一种脂肪组织来源的蛋白质,具有重要的生理功能。近年研究发现,RBP4在冠心病的发生发展过程中起着至关重要的作用。RBP4可能早期提示冠状动脉粥样硬化的发生,并为冠状动脉的早期病变发出危险信号。本文就RBP4对于早期提示冠心病的近年研究成果进行综述。     

视黄醇结合蛋白4与心血管疾病的研究

<正>人体脂肪组织不但具有储存能量的功能,而且还是一个重要的内分泌器官,它可以分泌大量的脂肪细胞因子,如网膜素、脂联素、视黄醇结合蛋白(RBP)等,还可以分泌许多生物活性物质。其中RBP-4是较新发现的一种脂肪细胞因子,有研究表明它在脂肪代谢和能量平衡中起重要作用。当前研究认为脂肪组织所分泌的脂肪细胞因子在肥胖、心血管疾病、代谢综合征及2型糖尿病等疾病中发挥着重要作用。本文对RBP-4在心血管疾病中所起     

Retinol-binding protein 4 : a possible role in cardiovascular complications

BACKGROUND AND PURPOSE

Retinol-binding protein 4 (RBP4) is an adipocyte-secreted hormone proposed to link obesity with insulin resistance. However, the role of RBP4 in cardiovascular complications is yet to be fully understood. The present study is aimed to decipher the association between RBP4 with pro-inflammatory cytokines and low-density lipoprotein (LDL) cholesterol in diet-induced obese and hyperlipidaemic mice. To understand the correlation, rimonabant, an anti-obesity drug, has been used to relieve the atherosclerotic predisposition.

EXPERIMENTAL APPROACH

Adipose and/or aortic tissue expressions of RBP4, pro-inflammatory cytokine genes and circulating LDL levels were measured in high fat (HF)-fed female C57BL/6 and high cholesterol (HC)-fed apolipoprotein E3 (ApoE3) Leiden mice.

KEY RESULTS

Mice fed a HF diet had a significantly increased adipose expression of RBP4, TNF-α and monocyte chemoattractant protein 1 (MCP-1) and down-regulated adiponectin mRNA levels. A significant increase in aortic RBP4 and MCP-1 expression and circulating levels of LDL and C-reactive protein (CRP) was found in the ApoE3 mice fed a HC diet. Interestingly, rimonabant treatment lowered the elevated aortic RBP4, MCP-1 expressions and significantly reduced the serum levels of LDL, CRP, RBP4 and MCP-1.

CONCLUSION AND IMPLICATIONS

Our results indicate that RBP4 is positively associated with markers of inflammation in obese and pro-atherogenic conditions and could play a role in a predisposition to atherosclerosis. Furthermore, our results indicate that rimonabant may improve vascular function by modulating RBP4 along with pro-inflammatory cytokines.     

视黄醇结合蛋白4与冠心病的关系

目的研究视黄醇结合蛋白4(RPB4)与冠心病(CHD)之间的关系。方法研究对象78例,分为两组:正常对照组和冠心病组。测定血浆RPB4水平,采集有关数据。结果冠心病组血浆RPB4水平明显高于正常对照组[(44.72±16.98),(39.60±12.10),P<0.05]。相关分析显示血浆RBP4与腰围、腰臀比、BMI、TC、ln(TG)、FINS、FCP、ln(HOMA-IR)呈正相关。多元逐步回归分析,ln(TG)是血浆RBP4独立相关因素。结论血浆RBP4在冠心病的发病过程中起一定作用。     

MAPK对RBP4诱导炎性反应的调节机制及研究

目的探讨MAPK对视黄醇蛋白4(RBP4)诱导炎性反应的调节机制。方法利用大鼠胸主动脉内皮细胞作为研究对象,首先检测了RBP4对白细胞介素-2、白细胞介素-6以及TNF-α的mRNA水平的调节作用,其次,通过PI3K特异性抑制剂(wortmannin)作用下,检测PI3K的mRNA水平,同时检测RBP4对白细胞介素-2、白细胞介素-6以及TNF-α的mRNA水平的调节作用变化。结果 RBP4能够显著上调白细胞介素-2、白细胞介素-6以及TNF-α的mRNA水平(P<0.05)。在wortmannin作用下,PI3K的mRNA水平显著下调,白细胞介素-2、白细胞介素-6以及TNF-α的mRNA水平显著下调(P<0.05)。在过表达PI3K病毒作用下,白细胞介素-2、白细胞介素-6以及TNF-α的mRNA水平显著上升(P<0.05)。结论本实验初步研究得出MAPK对RBP4诱导的炎性反应具有调节作用。     

视黄醇结合蛋白4与肥胖、胰岛素抵抗的关系

目的 探讨视黄醇结合蛋白-4(RBP-4)水平与肥胖病人体重指数、胰岛素抵抗的关系.方法 选取我院(2009年3月- 2010年3月)内分泌科住院病人71例,其中肥胖36例(男孩19例,女孩17例),正常体重35例.测量体重、身高、腰围、血压等,并测定其血清RBP-4、空腹血糖及胰岛素水平,并计算HOMA-IR,分析血清RBP-4水平与体重指数、空腹血糖及胰岛素抵抗指数HOMA-IR之间的相关性.结果 相对于正常体重儿童,肥胖儿童的血清RBP4水平显著升高(P＜0.0l),且肥胖程度越高,RBP4水平越高,而减重后RBP4水平显著下降(P＜0.01).青春期儿童血清RBP4水平升高,血清RBP4水平无性别差异.多元回归分析剔除年龄、性别、青春发育阶段影响后,RBP4与肥胖程度、体重指数、胰岛素抵抗指数HOMA-IR有显著相关.结论 肥胖儿童血清RBP4水平升高,其水平与肥胖程度、体重指数BMI、胰岛素抵抗指数HOMA-IR显著相关.     

RBP4/TNF-α在冠心病患者血浆中的表达情况及与冠脉病变程度的相关性研究

目的 探讨视黄醇结合蛋白4(RBP4)和肿瘤坏死因子-α(TNF-α)水平与冠心病、冠脉病变程度的关系以及冠心病患者血浆RBP4和TNF-α 两者之间的相关性.方法 选择2015年12月—2017年2月至该院就诊并诊断为冠心病的90例患者临床资料.根据临床特点及结合冠脉造影的结果 分为:稳定型心绞痛(SAP)组28例、不稳定型心绞痛(UAP)组30例、急性心梗(AMI)组32例,另选该院体检健康者30例作为对照组;根据冠脉造影结果再将UAP组和AMI组患者分为单支病变组19例,双支病变组21例,三支病变组22例.采用酶联免疫吸附试验法(ELISA)检测各组患者血浆RBP4、TNF-α 的水平,分析冠心病不同类型及冠脉病变不同程度患者血浆中RBP4、TNF-α 变化趋势及两者之间的相关性,并采用SPSS17.0统计软件对所得数据进行分析.结果RBP4及TNF-α 水平在AMI、UAP、SAP及对照组四组间存在明显差异(P<0.05);RBP4与TNF-α 血浆水平在双支病变组与单支病变组及三支病变组与双支病变组相比呈现升高趋势,但三组血浆RBP4水平差异无统计学意义(P>0.05)、TNF-α 水平存在明显差异(P<0.05);冠心病患者血浆RBP4与TNF-α 血浆水平呈正相关(r=0.906,P<0.001).结论 RBP4及TNF-α 可视为冠心病的重要危险因素,可反映冠心病及冠脉病变的严重程度.冠心病患者血浆RBP4与TNF-α 水平相关,提示RBP4可能通过调节炎性反应,参与冠心病的发生、发展.     

Stress and Obesity as Risk Factors in Cardiovascular Diseases: A Neuroimmune Perspective

Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases.     

Effects of IL-22 on cardiovascular diseases

Interleukin-22 (IL-22), which belongs to the IL-10 family, is an alpha helix cytokine specifically produced by many lymphocytes, such as Th1, Th17, Th22, ILCs, CD4+ and CD8+ T cells. In recent years, more and more studies have demonstrated that IL-22 has an interesting relationship with various cardiovascular diseases, including myocarditis, myocardial infarction, atherosclerosis, and other cardiovascular diseases, and IL-22 signal may play a dual role in cardiovascular diseases. Here, we summarize the recent progress on the source, function, regulation of IL-22 and the effects of IL-22 signal in cardiovascular diseases. The study of IL-22 will suggest more specific strategies to maneuver these functions for the effective treatment of cardiovascular diseases and future clinical treatment.     

Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure.

Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T(4)) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T(4), and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, n = 82), for total T(4) (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 0.34 +/- 0.19 microg/mg (n = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT(4) (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = -0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). The concentrations of TTR, TT(4), and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by PB: These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.     

Endothelin-1 (1-31): from chymase-dependent synthesis to cardiovascular pathologies

The mast cell-derived serine protease chymase is importantly involved not only in degradation, but in synthesis of bioactive peptides as well. Several studies suggest that chymase is the predominant enzyme in the production of angiotensin II (Ang II) from angiotensin-I in interstitial tissues. Interestingly, chymase has also been suggested to mature endothelin-1 (ET-1) from its precursor, big-ET-1 in vitro. The lack of availability of specific chymase inhibitors, beyond the chymotrypsin-like inhibitor chymostatin, currently hampers the investigation of the chymase/ET-1/Ang II paradigm in physiology and cardiovascular diseases. Nonetheless, the recent advent of highly selective chymase inhibitors is shedding new light on the role of this enzymatic pathway in the several inflammatory prone vascular diseases as summarized in the present review. Considering increasing evidence towards significant interactions between Ang II and ET-1 in cardiovascular diseases, the present review will address the role of chymase in the production of those two peptides. Whether chymase-dependent production of ET-1 plays an important role in cardiovascular pathologies will also be discussed.