Chemerin研究进展

Chemerin是一种免疫调节因子,在炎性反应相关的一系列蛋白酶作用下可对白细胞产生趋化作用,并参与炎性反应.同时chemerin也是一种调节脂肪细胞生成、代谢及葡萄糖稳态的脂肪因子,其参与了肥胖及代谢综合征的发生、发展.近年来研究发现chemerin对糖尿病及代谢综合征具有一定的诊断意义,且其有可能成为治疗相关疾病的新靶点.     

Chemerin 与阻塞性睡眠呼吸暂停低通气综合征

OSAHS 发病率逐年升高,已成为危害人类健康的主要疾病之一,OSAHS 的发病机制目前尚未完全阐明。chemerin 作为一种新的脂肪因子,可通过自分泌、旁分泌、内分泌等形式作用于机体脂肪细胞,促进脂肪细胞的分化、脂解,影响糖脂代谢;并可参与机体的血压调节、免疫应答及炎症反应等,与 OSAHS 的发生有密切的联系。本文就脂肪因子 chemerin 与 OSAHS 的相关性进行简要综述。     

脂肪因子Chemerin与胰岛素抵抗及心血管疾病的关联

胰岛素抵抗(IR)处于心血管疾病危险因素中的核心地位。近年许多研究显示脂肪因子chemerin与IR密切相关,chemerin及其受体可以通过多种信号途径参与IR的发生和发展,而IR与心血管疾病的发生、发展、治疗及预后相关。以chemerin作为新的靶点,采取多种措施改善IR,将会对未来预防和治疗心血管疾病有重要意义。     

重组人脂肪因子Chemerin对巨噬细胞凋亡影响及其机制的研究

目的:观察脂肪因子Chemerin是否参与调节巨噬细胞凋亡,并探讨其可能的机制。方法:100nmol/L佛波酯(PMA)诱导THP-1单核细胞分化为巨噬细胞,随机分组,在含1%胎牛血清的DMEM培养基中,加入100mg/L乙酰低密度脂蛋白及10mg/L胆固醇乙酰转移酶抑制剂-58035,促进游离胆固醇(FC)聚集。在不同浓度重组chemerin的作用下与FC聚集的巨噬细胞共孵育。以JNK阻断剂和P38MAPK阻断剂进行干预,Annexin-V和PI双染后用流式细胞仪检测巨噬细胞凋亡。结果:重组人Chemerin能显著增加巨噬细胞凋亡率,并且这种作用随chemerin浓度的增加而增加[巨噬细胞凋亡率对照组(19.04±0.39)%、重组chemerin0.1μg/L组(22.77±0.86)%、10μg/L组(26.37±1.06)%、500μg/L组(33.44±0.87)%]。以JNK阻断剂和P38MAPK阻断剂干预后,重组chemerin组巨噬细胞凋亡率下降幅度高于中和chemerin组[重组chemerin组和中和chemerin组应用JNK阻断剂前后的差值分别为(9.85±0.34)%和(6.13±1.09)%;重组chemerin组和中和chemerin组在应用P38MAPK阻断剂前后的差值分别为(11.82±0.60)%和(7.65±0.83)%]。结论:重组人Chemerin能显著增加巨噬细胞凋亡,并且JNK及P38MAPK信号通路参与此凋亡过程。     

3T3-L1前脂肪细胞烟碱样胆碱能受体α7亚型功能状态对chemerin及其受体chemerinR基因表达的影响

目的观察3T3-L1脂肪前体细胞诱导分化过程中chemerin及其受体(chemerinR)基因表达水平的变化趋势,及脂肪细胞中非神经元型胆碱能系统尤其是烟碱样胆碱能受体α7功能状态对前脂肪细胞和诱导分化成熟脂肪细胞中新型促脂解脂肪因子chemerin和其受体基因表达水平的影响,旨在探讨脂肪细胞中非神经元型胆碱能系统对脂解影响的分子机制。方法"经典激素鸡尾酒法"(1-甲基3-异丁基黄嘌呤 胰岛素 地塞米松 胎牛血清 DMEM/F12培养基)诱导3T3-L1前脂肪细胞分化,并于分化进程中0h,6h,12h,1d,3d,6d和9d收集细胞并提取总RNA,RT-PCR技术检测chemerin、chemerinR mRNA时序性变化规律。并加入不同浓度(10-8mol/L、10-6mol/L和10-4mol/L)的烟碱样乙酰胆碱受体α7激动剂氯化胆碱和拮抗剂甲基牛扁亭碱,分别处理3T3-L1前脂肪细胞和诱导分化成熟的脂肪细胞12 h、24 h和36 h后,抽提总RNA,RT-PCR检测chemerin、chemerinR mRNA的表达。结果①在诱导3T3-L1前脂肪细胞分化成熟的过程中,二者基因均呈现逐渐升高趋势,至分化末期表达水平最高。②与相应作用时点的空白对照组比较,氯化胆碱能显著下调前脂肪细胞chemerin、chemerinR mRNA和成熟脂肪细胞中chemerin mRNA水平;甲基牛扁亭碱则明显上调前脂肪细胞chemerin、chemerinR mRNA和成熟脂肪细胞中chemerin mRNA水平,上述两种干预均对成熟脂肪细胞中chemerinR mRNA水平无明显影响。③且在相同浓度、相同时间干预下,烟碱样胆碱能受体α7特异性激动剂或拮抗剂对前脂肪细胞中chemerin、chemerinR mRNA水平影响均较诱导分化成熟脂肪细胞组显著。结论前脂肪细胞上烟碱样胆碱能受体α7,很可能是介导前脂肪细胞固有胆碱能系统发挥生物学效应的重要物质,除参与脂解的直接调控外,还可能通过影响自身脂肪因子的表达实现间接调节。     

高血压病患者血清chemerin与颈动脉粥样硬化的关系

目的 研究高血压患者血清chemerin水平与颈动脉粥样硬化的相关性.方法 选择80例无糖尿病病史的高血压病患者和40例体检正常者,收集一般临床资料,测量血压、腰围、臀围,测定空腹血糖、空腹胰岛素和超敏C-反应蛋白（hs-CRP）等生化指标,采用ELISA法测定血清chemerin水平,用胰岛素抵抗指数（IRI）作为胰岛素敏感性评价指标,颈动脉超声检测颈动脉内-中膜平均厚度（IMT）.将高血压病患者分为斑块组（IMT≥1.5 mm）40例和无斑块组（IMT＜1.5 mm）40例.结果 腰围、低密度脂蛋白、空腹胰岛素、IRI、hs-CRP、chemerin及颈动脉IMT,高血压颈动脉斑块组、无颈动脉斑块组和对照组之间差异有统计学意义（P＜0.05）.高血压斑块组及无斑块组患者血浆ehemerin水平均与hs-CRP、IRI及IMT呈正相关（P＜0.05）.经单因素及多因素分析发现,IRI、hs-CRP及ehemerin与高血压发生颈动脉粥样硬化密切相关（OR值分别是2.134、2.248、1.101,P均＜0.05）.结论 高血压病患者chemerin与胰岛素抵抗及超敏C-反应蛋白密切相关,且chemerin是高血压病患者发生颈动脉粥样硬化的危险因素,提示chemerin可能通过胰岛素抵抗及非特异性炎症在高血压颈动脉粥样硬化发病过程中起重要作用.     

脂肪因子趋化素与心血管疾病关系的研究进展

脂肪是三大供能物质之一,脂肪组织则是人体重要的能量仓库,脂肪因子的发现也揭示了脂肪组织的另一个重要身份——内分泌器官。脂肪组织分泌的细胞因子称为脂肪因子,脂肪因子趋化素(chemerin)是近年新发现的脂肪因子,研究发现chemerin水平与高血压、冠状动脉粥样硬化性心脏病及心力衰竭等疾病密切相关。该文就近年来研究发现的chemerin在心血管疾病中的作用机制进行综述。     

Apelin研究进展

Apelin是孤独G蛋白偶联受体APJ的内源性配体,在组织中分布广泛,具有降低血压、增强心肌收缩力、调节水盐平衡、促进垂体激素释放及调节免疫等多种生物学效应。最近的研究表明,apelin是一种脂肪细胞因子,其表达与肥胖明显相关,可抑制高血糖刺激的胰岛素分泌。因此,apelin是一种重要的生理调节肽。     

脂肪因子在肺癌发生发展机制中的研究进展

<正>研究表明由脂肪组织分泌的脂肪因子参与了慢性阻塞性肺疾病、肺癌、哮喘等呼吸系统疾病的发生发展过程。同时,肺癌又是目前全球最常见、疾病负担最重的恶性肿瘤之一。本文介绍瘦素、脂联素、visifan、chemerin在肺癌中的生物学作用。瘦素(Leptin)瘦素是1994年第一个被发现的脂肪激素[1],其不但参与身体的脂肪代谢还参与其它的生理调节反应,有促进血管生成、促有丝分裂和免疫调节的特     

Apelin在心血管系统及脂肪胰岛轴中的作用

Apelin是孤儿G蛋白耦联受体APJ的的内源性配体,也是由脂肪细胞分泌的一个新的脂肪细胞因子。其通过与APJ受体结合发挥多种生物学效应,如舒张/收缩血管、增强心肌收缩力、调节体液平衡、调节胰岛素分泌等。现就其在心血管系统及脂肪胰岛轴中的作用做简要综述。     

5-羟色胺7受体与功能性胃肠病

5-羟色胺及其受体广泛分布于胃肠道.5-羟色胺7受体有多种生理功能,对胃肠运动和感觉的调控有重要作用.对5-羟色胺7受体的分子结构、组织分布、生理功能已进行了相关研究,并日益受到重视.深入开展5-羟色胺7受体在消化道的生理功能和功能性胃肠病中的病理机制的研究,有助于进一步阐明功能性胃肠病的发病机制及开发新的有效治疗药物.     

血管内皮生长因子受体1在血液系统肿瘤中的研究进展

新生血管形成在血液系统肿瘤的发生、发展和预后中起重要作用,血管内皮生长因子(VEGF)作为血管生成调控因子,起着关键作用.已经证实VEGF及其受体在多种肿瘤包括血液系统肿瘤中高表达并与疾病的分期、预后相关,针对VEGF及其受体为靶点的抗血管治疗也取得初步的成功.     

Implication of the purinergic system in alcohol use disorders

In the central nervous system, adenosine and adenosine 5'-triphosphate (ATP) play an important role in regulating neuronal activity as well as controlling other neurotransmitter systems, such as, GABA, glutamate, and dopamine. Ethanol increases extracellular adenosine levels that regulate the ataxic and hypnotic/sedative effects of ethanol. Interestingly, ethanol is known to increase adenosine levels by inhibiting an ethanol-sensitive adenosine transporter, equilibrative nucleoside transporter type 1 (ENT1). Ethanol is also known to inhibit ATP-specific P2X receptors, which might result in such similar effects as those caused by an increase in adenosine. Adenosine and ATP exert their functions through P1 (metabotropic) and P2 (P2X-ionotropic and P2Y-metabotropic) receptors, respectively. Purinergic signaling in cortex-striatum-ventral tegmental area (VTA) has been implicated in regulating cortical glutamate signaling as well as VTA dopaminergic signaling, which regulates the motivational effect of ethanol. Moreover, several nucleoside transporters and receptors have been identified in astrocytes, which regulate not only adenosine-ATP neurotransmission, but also homeostasis of major inhibitory-excitatory neurotransmission (i.e., GABA or glutamate) through neuron-glial interactions. This review will present novel findings on the implications of adenosine and ATP neurotransmission in alcohol use disorders.     

p75 神经营养因子受体在心血管系统中的作用

p75神经营养因子受体属于神经营养因子的受体之一。越来越多的研究表明,p75NTR在心血管系统自主神经中发挥重要的作用,不仅促进交感神经的生长发育,还调节心脏神经递质的释放。p75NTR还抑制新生血管形成,具有一定的抗血管生成作用,且介导平滑肌细胞凋亡,加重血管粥样硬化损伤。p75NTR这些特性表明其抑制剂存在重要的治疗潜能,或许能够改善缺血所致的损伤,如冠心病、急性心肌梗死、周围血管病变等。     

Conservation of progesterone hormone function in invertebrate reproduction

Steroids play fundamental roles regulating mammalian reproduction and development. Although sex steroids and their receptors are well characterized in vertebrates and several arthropod invertebrates, little is known about the hormones and receptors regulating reproduction in other invertebrate species. Evolutionary insights into ancient endocrine pathways can be gained by elucidating the hormones and receptors functioning in invertebrate reproduction. Using a combination of genomic analyses, receptor imaging, ligand identification, target elucidation, and exploration of function through receptor knockdown, we now show that comparable progesterone chemoreception exists in the invertebrate monogonont rotifer Brachionus manjavacas, suggesting an ancient origin of the signal transduction systems commonly associated with the development and integration of sexual behavior in mammals.     

Calcium acts as a first messenger through the calcium-sensing receptor in the cardiovascular system

It is well known that calcium is an important second messenger in the cardiovascular system. However, recent studies suggest that, in addition to its many functions as an intracellular messenger, Ca(2+) may also be an extracellular first messenger through the calcium-sensing receptor (CaR). The CaR belongs to family C of the G-protein-coupled receptors, which are also known as seven transmembrane domain receptors. The CaR receptor is expressed in all major organs involved in Ca(2+) homeostasis. Furthermore, increasing evidence suggests that the CaR is also involved in regulating various cellular functions in tissues not involved in Ca(2+) homeostasis. Recently, expression of a functional CaR has also been reported in crucial components of the cardiovascular system. It has previously been shown that the CaR is functionally expressed in the atria and ventricle of the rat heart. In blood vessels, the CaR protein was first reported in perivascular nerves of rat mesenteric resistance arteries, and was proposed to modulate myogenic tone in the arteries. Since then, the CaR has been detected in homogenates of whole vessels from rat subcutaneous small arteries and in endothelial cells from rat mesenteric and porcine coronary arteries. Furthermore, a recent report demonstrated that the CaR is present in endothelial cells from human aorta and that it stimulates production of nitric oxide in these cells. Taken together, these results indicate that the CaR present in blood vessels may have a physiological role in modulation of arterial blood pressure. This review discusses CaR expression and function, with a focus on the role of the CaR in the cardiovascular system.     

Network integration of the adrenergic system in cardiac hypertrophy

Adrenergic receptors play a pivotal role in regulating cardiac function in response to a constantly changing environment. Altered alpha and beta adrenergic receptor signaling in vivo is associated with cardiac hypertrophy and failure. This review focuses on the different roles of adrenergic receptors in regulating cardiac function under normal and pathological conditions. Understanding the signaling mechanisms of these receptors in the context of the heart is likely to provide a better therapeutic approach towards treatment of heart failure.     

Orexins and their receptors from fish to mammals: a comparative approach

Although recently discovered, orexins have been rapidly established as important neuropeptides in regulating physiological processes including food intake, sleep/wake cycles and reproduction through binding to two class B G protein-coupled receptors (OX1R and OX2R). To date, a handful of sequences for orexins and their receptors ranging from fish to mammalian species have been identified, allowing a glimpse into their evolution. Structurally, the genetic and molecular organization of the peptides and receptors amongst vertebrates are highly similar, underlining the strong evolutionary pressure that has been exerted to preserve structure and ultimately function. Furthermore, the absence of invertebrate orexin-like sequences suggests early vertebrates as the origin from which orexins evolved. With respect to the receptors, OX2R is probably evolutionary more ancient whilst OX1R is specific to mammalian species and evolved only during this later lineage. In common to all vertebrates studied, the hypothalamus remains to be the key brain region in which orexinergic neurons and fibers are localized in, establishing orexin to be an important player in regulating physiological processes especially those related to food intake and energy metabolism. To allow better understanding of the evolution of orexins and their receptors, this review will provide a comparative approach to their structures and functions in vertebrates.