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内分泌器官肾上腺可合成类固醇激素、儿茶酚胺类激素等有效物质,协助维持神经-免疫-内分泌系统稳态。中药因其多成分、多靶点、多途径的特点而被广泛关注,其在内分泌系统疾病、代谢性疾病等的治疗中具有独特优势,但其对肾上腺作用的相关研究较少,仍有待深入探索。综述有关中药对肾上腺形态和功能的调控作用,以及中药通过调控肾上腺功能协助治疗类风湿性关节炎和抑郁症的研究进展,为进一步丰富中药与内分泌领域研究提供参考。 相似文献
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Folkman于1970年首次提出了肿瘤血管生成理论,并认为肿瘤的生长和转移都依赖于新生血管的形成[1]。研究发现众多的促血管生成因子和抑制因子在肿瘤血管生成过程中起调控作用,血管内皮生长因子(VEGF)是其中很重要的一类。VEGF是血管生成的主要调控因子,可特异性地作用于血管内皮细胞,在体外及体内都是内皮细胞增殖和迁移的强烈刺激因素,对肿瘤血管的形成具有重要的意义,是实体瘤生长和进展过程中重要的调节因 相似文献
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线粒体是一类高度活跃的细胞器,在细胞能量代谢等生命活动中具有重要的作用。线粒体生成,即线粒体的增殖以及线粒体系统合成和个体合成的过程。近年来研究提示,线粒体生成与线粒体的功能调节密切相关,而过氧化物酶体增殖物激活受体γ辅激活因子-1α(peroxisome proliferator-ac-tivated receptor gamma co-activator,PGC-1α)可能是线粒体生成的关键调控因子。特别是在心血管系统中,PGC-1α信号途径调控的线粒体生成可能是维持和修复心肌细胞和血管内皮细胞等心血管系统细胞线粒体功能的主要机制之一,在心力衰竭、心肌肥大、糖尿病心血管并发症等心血管疾病的发生与发展过程中具有重要作用。PGC-1α作为心血管疾病疾病预防和治疗的潜在靶标,将有可能为心血管疾病的防治提供新的策略。 相似文献
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神经类固醇对学习记忆与应激性情绪反应的调控作用 总被引:1,自引:0,他引:1
近年来焦虑、抑郁等精神性疾患的发病率呈上升趋势,患者体内神经内分泌系统功能系乱,多种类固醇激素、神经肽等浓度失衡,其中神经类固醇对机体内环境的稳定起重要调控作用。本文综述了神经类固醇的生成、代谢以及神经类固醇对学习记忆和应激性情绪反应的调控作用。并对其作用机制进行了探讨。 相似文献
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先天性肾上腺增生(CAH)是由于肾上腺类固醇代谢生物合成过程中先天性缺乏所致。缺乏使产生的肾上腺类固醇没有效应。考的松前驱物过度生成和累积,其中一些可产生雄性激素效应。于是肾上腺皮质增生。雄性激素形成过度将抑制胚胎生殖系统沿着女性方向分化,从而导致女性男性化。约30%病例,无机盐皮质激素类形成也受到影响,引 相似文献
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《中国药理学与毒理学杂志》2017,(5)
GATA1是一种含有2个锌指结构的转录因子,参与红细胞、巨核细胞、肥大细胞和嗜酸性粒细胞的正常生物学功能。研究发现,GATA1转录因子在巨核细胞分化中起重要调控作用,其表达异常可能引起血小板减少症、白血病和骨髓纤维化等血液系统疾病。本文就转录因子GATA1调控巨核细胞分化的机制、GATA1表达异常和血液系统疾病的关系及可能靶向转录因子GATA1药物的研究进展予以综述。 相似文献
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目的探讨帕博利珠单抗致原发性肾上腺功能减退的发病机制及管理措施。方法分析1例帕博利珠单抗致原发性肾上腺功能减退的诊疗经过,结合文献分析,阐述帕博利珠单抗与原发性肾上腺功能减退不良反应的因果关系、发生率、发病机制和处理措施。结果患者静脉使用帕博利珠单抗6个月后出现明显乏力、体力差、食欲差、皮肤变黑症状。入院行实验室检查8AM血清促肾上腺皮质激素(ACTH)16.7 pmol·L-1,8AM血清皮质醇<25.7 nmol·L-1,考虑为帕博利珠单抗致原发性肾上腺功能减退。建议暂停帕博利珠单抗治疗,口服醋酸泼尼松片每日2次,每次5 mg用于类固醇激素替代治疗,1周后患者症状好转出院。院外逐渐减少醋酸泼尼松片至5 mg·d-1维持剂量。结论对帕博利珠单抗致原发性肾上腺功能减退,应根据不良反应分级标准采取相应的分级处理措施。 相似文献
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缺氧诱导因子-1生物学特性的研究新进展 总被引:2,自引:0,他引:2
李国青 《实用医药杂志(山东)》2005,22(8):749-750
缺氧诱导因子-1(Hypoxia inducible factor-1,HIF-1)是在缺氧条件下广泛存在于哺乳动物和人体内的一种转录因子,它最先由Semenza于1992年在缺氧诱导的细胞核抽提物中发现。目前已发现HIF-1可调控一系列靶基因的表达,具有许多重要的生物学效应,其已成为近年来的研究热点。本文主要就HIF-1在结构、功能调节、靶基因及其调控方面的研究新进展综述如下。 相似文献
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Del Tredici AL Andersen CB Currier EA Ohrmund SR Fairbain LC Lund BW Nash N Olsson R Piu F 《Molecular pharmacology》2008,73(3):900-908
Steroidogenic factor SF-1, a constitutively active nuclear hormone receptor, is essential to the development of adrenal and gonadal glands and acts as a shaping factor of sexual determination and differentiation. Its effects are exerted primarily through the control of the synthesis of steroid hormones. The functional cell-based assay Receptor Selection and Amplification Technology (R-SAT) was used to identify potent and selective SF-1 inverse agonists through the screening of a chemical library of drug-like small-molecule entities. Among them, 4-(heptyloxy)phenol (AC-45594), a prototype inverse agonist lead, was used to show that SF-1 constitutive activity can be pharmacologically modulated by a synthetic ligand. In a physiological system of endocrine function, the expression of several reported SF-1 target genes, including SF-1 itself, was inhibited by treatment with AC-45594 and analogs. Thus, pharmacological modulation of SF-1 is critical to its function as an endocrine master regulator and has potentially important consequences to diseases in which SF-1 activity is critical. 相似文献
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乳腺癌是女性最常见的恶性肿瘤。BRCA1是重要的乳腺癌易感基因,亦是一种抑癌基因。它参与了细胞周期的调节,DNA损伤修复,基因的转录调控等功能。BRCAl基因的突变与家族性乳腺癌的发生密切相关,而BRCA1蛋白在散发性乳腺癌中的表达水平降低,提示其在散发性乳腺癌中也有重要作用。该文将对BRCA1的基因突变,甲基化和多态性等遗传学改变与乳腺癌的易感性,治疗和预后作了综述。了解BRCA1与乳腺癌的发生、发展及预后,对于最终发现治疗乳腺癌的新方法有着重要价值 相似文献
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Whitby RJ Dixon S Maloney PR Delerive P Goodwin BJ Parks DJ Willson TM 《Journal of medicinal chemistry》2006,49(23):6652-6655
We report the identification of substituted cis-bicyclo[3.3.0]-oct-2-enes as small molecule agonists of subfamily V orphan nuclear receptors (NR5A), liver receptor homolog-1 (LRH-1) and steroidogenic factor-1 (SF-1). Using fluorescence resonance energy transfer (FRET)-based biochemical assays, compound 5a (GSK8470) was identified as a high-affinity ligand for LRH-1 and SF-1. In liver cells, 5a increased the expression of the LRH-1 target gene small heterodimer partner (SHP). Synthesis of analogues modified at three positions led to the development of compounds with functional selectivity between LRH-1 and SF-1. 相似文献
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Whitby RJ Stec J Blind RD Dixon S Leesnitzer LM Orband-Miller LA Williams SP Willson TM Xu R Zuercher WJ Cai F Ingraham HA 《Journal of medicinal chemistry》2011,54(7):2266-2281
The crystal structure of LRH-1 ligand binding domain bound to our previously reported agonist 3-(E-oct-4-en-4-yl)-1-phenylamino-2-phenyl-cis-bicyclo[3.3.0]oct-2-ene 5 is described. Two new classes of agonists in which the bridgehead anilino group from our first series was replaced with an alkoxy or 1-ethenyl group were designed, synthesized, and tested for activity in a peptide recruitment assay. Both new classes gave very active compounds, particularly against SF-1. Structure-activity studies led to excellent dual-LRH-1/SF-1 agonists (e.g., RJW100) as well as compounds selective for LRH-1 (RJW101) and SF-1 (RJW102 and RJW103). The series based on 1-ethenyl substitution was acid stable, overcoming a significant drawback of our original bridgehead anilino-substituted series. Initial studies on the regulation of gene expression in human cell lines showed excellent, reproducible activity at endogenous target genes. 相似文献
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The transient receptor potential vanilloid 1 (TRPV1) channel has been a topic of great interest, since its discovery in 1997. It is a homotetrameric non-selective cation channel predominantly expressed in a population of sensory neurons and its involvement in different modalities of pain has been extensively studied. However, TRPV1 has also been shown to be expressed in non-sensory neurons and non-neuronal cells. TRPV1 is considered as a potential target for drug development, based on its tissue distribution and its role in physiological functions. Here, we summarize the evidences for disease-related alterations in TRPV1 expression and function and review the current perspectives for the therapeutic potential of TRPV1 agonists and antagonists in the treatment of a wide range of diseases. 相似文献
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Asperlin is a fungal metabolite isolated from Aspergillus sp. SF-5044. In the present study, we isolated asperlin from the marine-derived fungus Aspergillus sp. SF-5044 and demonstrated that it inhibited inducible nitric oxide synthase (iNOS) expression, reduced iNOS-derived NO, suppressed cyclooxygenase (COX)-2 expression, and reduced COX-derived prostaglandin (PG) E? production in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. Similarly, asperlin reduced the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In addition, asperlin inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of p65 caused by the stimulation of LPS in RAW264.7 macrophages. Furthermore, asperlin induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 and increased HO activity in RAW264.7 macrophages. The effects of asperlin on the LPS-induced expression of iNOS and COX-2 and production of NO, PGE?, TNF-α, and IL-1β were partially reversed by a HO-1 inhibitor, tin protoporphyrin. These findings suggest that asperlin-induced HO-1 expression plays a role in the anti-inflammatory effects of asperlin in macrophages. 相似文献
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Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters 总被引:17,自引:0,他引:17
The 190 kDa multidrug resistance protein 1 (MRP1/ABCC1) is a founding member of a subfamily of the ATP binding cassette (ABC) superfamily of transport proteins and was originally identified on the basis of its elevated expression in multidrug resistant lung cancer cells. In addition to its ability to confer resistance in tumour cells, MRP1 is ubiquitously expressed in normal tissues and is a primary active transporter of GSH, glucuronate and sulfate conjugated and unconjugated organic anions of toxicological relevance. Substrates include lipid peroxidation products, herbicides, tobacco specific nitrosamines, mycotoxins, heavy metals, and natural product and antifolate anti-cancer agents. MRP1 also transports unmodified xenobiotics but often requires GSH to do so. Active efflux is generally an important aspect of cellular detoxification since it prevents the accumulation of conjugated and unconjugated compounds that have the potential to be directly toxic. The related transporters MRP2 and MRP3 have overlapping substrate specificities with MRP1 but different tissue distributions, and evidence that they also have chemoprotective functions are discussed. Finally, MRP homologues have been described in other species including yeast and nematodes. Those isolated from the vascular plant Arabidopsis thaliana (AtMRPs) decrease the cytoplasmic concentration of conjugated toxins through sequestration in vacuoles and are implicated in providing herbicide resistance to plants. 相似文献