肝细胞生长因子与哮喘

肝细胞生长因子(HGF)是一个多功能的细胞生长因子,具有保护气道上皮、抗细胞凋亡、抑制胶原组织沉积等作用,也是为数不多的抗组织纤维化的细胞因子之一。有实验证实HGF对哮喘大鼠的气道上皮有保护性作用,并可以改善气道组织重建、促进气道小血管的生成等。目前,哮喘的发生发展过程和机制仍不明确,治疗方法也在探索当中,HGF有可能成为一个新的研究哮喘机制和治疗哮喘的方法。     

肝细胞生长因子调控上皮细胞-间充质细胞转换改善胆管纤维化的机制研究

目的以上皮细胞-间充质细胞转换(epithelial-mesenchymal transition,EMT)在胆道闭锁(biliary atresia,BA)肝外胆管纤维化中的作用及其调节机制为切入点,探讨转化生长因子-β1(transforming growth factor-β1,TGF-β1)对肝外胆管EMT的诱导作用,以及肝细胞生长因子(hepatocyte growth factor,HGF)通过调控EMT来改善肝外胆管纤维化的作用机制。方法提取和培养BALb/c小鼠肝外胆管肝外胆管上皮细胞,按照研究目的不同,将第3次传代后的肝外胆管上皮细胞分为不添加生长因子的正常对照组、添加TGF-β1诱导EMT的TGF-β1组、添加HGF+TGF-β1的HGF干预组、仅添加HGF的HGF对照组和添加TGF-β1+HGF+SU11274的HGF抑制组。用蛋白免疫印记实验检测各组上皮细胞标志物CK19、E-cad和间质细胞标志物α-SMA和S100A4的表达情况。结果蛋白印迹实验显示,对照组CK19、E-cad、α-SMA和S100A4的表达量分别为1.31±0.02、0.90±0.05、0...     

肝细胞生长因子及其受体与肾脏疾病

1984年,Russell等在大鼠血浆中发现一种可刺激大鼠肝脏DNA合成的阳离子交换剂多肽,并称之为肝细胞生长因子(HGF).在随后的20余年中,人们对HGF的研究不断深入,目前认为HGF是一种多效性细胞因子,在促有丝分裂、细胞移动、血管生成、造血、抗凋亡、抗纤维化、修复组织损伤和抑制肿瘤细胞生长等多方面发挥苇要生物学功能.     

结缔组织生长因子与儿童肝纤维化的研究进展

肝纤维化是继发于肝脏炎症或损伤后组织修复的代偿反应,以细胞外基质增加为特征,同时伴有肝实质的广泛破坏、再生,导致肝小叶和肝血管结构的紊乱.结缔组织生长因子是一种在器官纤维化过程中起关键作用的细胞因子,与许多组织器官纤维化发生、发展密切相关,受到广泛关注,有望成为抗纤维化治疗的重要靶位.该文就结缔组织生长因子与儿童肝纤维化的研究进展进行综述.     

TGF-β与肝细胞生长因子在儿童原发性局灶节段性肾小球硬化肾组织中的表达

目的：通过检测转化生长因子β(TGF-β)和肝细胞生长因子(HGF)在儿童原发性局灶节段性肾小球硬化（FSGS）肾组织中的表达,了解它们在FSGS中的作用。方法：选择肾活检明确诊断为原发性FSGS肾组织标本共33 例,其中FSGS不伴肾小管间质病变6 例,为实验1 组;FSGS伴肾小管间质病变27 例,为实验2 组;同期因孤立性血尿入院肾活检,病理证实无显著异常改变的肾组织标本共7 例,为对照组。采用免疫组化法检测TGF-β和HGF在3 组肾组织中的表达。结果：TGF-β和HGF在3 组中均有表达,但组间差异有统计学意义（P＜0.01）。其中两个实验组的TGF-β和HGF的表达均较对照组明显增加（P<0.01）,实验2组TGF-β的表达量高于实验1组,HGF的表达量却低于实验1组。肾小管间质指数与TGF-β的表达呈正相关,相关系数是0.763,P<0.01;与HGF的表达呈负相关,相关系数是-0.461,P<0.05。TGF-β和HGF在FSGS肾组织中表达呈负相关,相关系数-0.425,P<0.05。结论：TGF-β和HGF在儿童原发性FSGS肾组织中的表达增加;TGF-β随着 FSGS病变进展,在肾组织中表达量增加,与肾小管间质向纤维化发展相关;HGF的表达相反,与抑制肾小管间质纤维化的作用有关。［中国当代儿科杂志,2010,12（8）：630-633］     

缬沙坦恢复哮喘大鼠气道肝细胞生长因子的生成及其意义

目的：探讨血管紧张素受体拮抗剂(AT1)缬沙坦,对恢复哮喘大鼠气道肝细胞生长因子(HGF)的生成与哮喘气道重塑的关系和意义。方法：SD清洁级大鼠32只,体重在100±10g,随机分为4组:A组:正常对照组,B组:卵蛋白(OVA)激发2周组,C组:OVA激发4周组,D组:OVA激发4周后缬沙坦干预组。用免疫组化法测定各组大鼠气道的HGF,AngII和TGF-β1的表达变化,苏木精-伊红染色观察气道病理变化。结果：A组HGF较B组有明显差异[(5.49±1.34)%vs(10.69±0.96)%,P<0.05],C组为(11.85±0.87)%,较A组升高(P<0.05),D组为(15.58±1.06)%,较B组、C组升高。AngII和TGF-β1的表达则随着OVA激发时间的延长而增加,在使用缬沙坦后两者都明显下降。经抗原致敏和激活的大鼠气道上皮脱落炎性细胞堆积呈现明显的病理改变,而缬沙坦干预组的病理改变较轻,上皮细胞较完整,炎性细胞和纤维细胞较少。结论：①HGF随着气道重塑变化浓度有所改变,说明早期HGF即有保护气道作用,和TGF-β1呈负相关性,有拮抗纤维化的作用;②AT1可改善气道重塑过程,可能是通过升高气道HGF水平达到抗纤维化的作用。     

胆道闭锁与上皮间质转化机制的研究进展

胆道闭锁是危及婴幼儿生命的肝胆系统疾病,以肝内外胆管进行性炎症和纤维化为特征,导致胆汁淤积以及进行性肝纤维化和肝硬化,最终进展为肝功能衰竭,是婴幼儿时期肝移植的主要指征.Kasai手术的广泛开展,使胆道闭锁患儿获得更多的生存机会,但术后60％的患儿1年内需行肝移植,只有25％的患儿自体肝存活至10岁.证据表明上皮间质转化在胆管纤维化中扮演着非常重要的角色,并且TGF-β1表达增强与胆道闭锁发生具有一定的相关性;而肝细胞生长因子(HGF)可明显抑制纤维化促进因子TGF-β1的表达,从而抑制组织纤维化.本文就胆道闭锁可能的发病机制、上皮间质转化在组织纤维化中的作用、针对上皮间质转化的抗纤维化治疗以及胆道闭锁治疗方法的展望作一综述.     

IFN-γ在肺损伤纤维化中的研究进展

肺损伤纤维化是一个复杂的病理生理过程,近年来研究表明许多细胞因子参与了其反应,其中γ-干扰素(IFN-γ)是一类由活化的淋巴细胞分泌的在宿主防御系统中起重要作用的细胞因子。IFN-γ在肺损伤纤维化的病理过程中表达增加,并和白细胞介素-12、肿瘤坏死因子-α、白细胞介素-13、转化生长因子-β、结缔组织生长因子有相互调节作用。IFN-γ通过与细胞因子的相互作用抑制促纤维化细胞因子(转化生长因子-β及结缔组织生长因子)的表达、抑制细胞外基质的沉积而在肺及肺外器官中发挥其抗纤维化作用,本文就这方面的研究进展作一概述。     

肝细胞生长因子在哮喘大鼠气道内的表达及血管紧张素Ⅱ受体拮抗剂对其表达的影响

目的探讨哮喘大鼠发病过程中,肝细胞生长因子(HGF)在其气道内表达的变化及血管紧张素II受体AT1拮抗剂对其表达的影响。方法清洁级SD大鼠48只,随机分为正常对照组、卵蛋白(OVA)激发3 d组、OVA激发2周组、OVA激发4周组、OVA激发4周后使用AT1受体拮抗剂组、OVA激发4周后使用盐水对照组。观察OVA激发的不同时间、药物干预后哮喘大鼠气道的病理改变;免疫组化方法观察HGF、血管紧张素II(AngII)、转化生长因子(TGF)-β1表达的变化。结果HGF在OVA激发3 d即明显高于正常对照组(P<0.05),OVA激发2周HGF在气道中的表达水平最高,OVA激发4周时下降;AngII、TGF-β1表达水平随OVA激发时间的延长而持续上升;使用AT1受体拮抗剂后,气道HGF表达水平有所上升,而AngII、TGF-β1均下降,同时哮喘大鼠的气道重塑有所改善。结论HGF在哮喘发病过程中起保护作用,AngII、TGF-β1对HGF具有负向调节作用,AT1受体拮抗剂在一定程度上可提升内源性HGF表达,改善哮喘大鼠的气道重塑。     

胎盘绒毛组织及脐血中造血细胞生长因子对人胎盘造血功能的影响

目的检测胎盘绒毛组织多种造血细胞生长因子(HGF)含量,探讨其对胎盘造血的意义。方法分别取早孕(6- 8周)、中孕(16-22周)、足月妊娠(37-42周)胎盘绒毛组织2 g各30份、脐血清30份,测定上清液中各种HGF含量。结果早期妊娠各种HGF均已产生;FL-13、IL-3在胎盘绒毛组织中含量随着胎龄增加,各胎龄组间比较,均有显著差异(P均< 0.01)。7种HGF在胎盘和脐血中含量,均有显著差异(P均<0.01)。结论F-T3配体(FL)、干细胞因子(SCF)、G-CSF等7 种HGF均参与胚胎期造血,尤以FL、IL-3、SCF最为重要。     

Specifics of histopathological and genetical diagnosis and classification of lymphomas in children and adolescents

Malignant lymphoma along with leukemias account for nearly half of all malignancies arising in childhood and adolescence. The correct tissue-based histopathological diagnosis of lymphomas results from a close interdisciplinary exchange between pediatric oncologists and hematopathologists. We describe here relevant features of lymphoma subtypes arising in the young age group, Burkitt lymphoma, precursor/lymphoblastic lymphomas, anaplastic large cell lymphoma and diffuse large B-cell lymphoma as well as primary mediastinal B-cell lymphoma and the rare pediatric follicular lymphomas. Special focus is put on specific diagnostic difficulties as well as new insights into biological features of pediatric lymphomas in comparison with their adult counterpart. In addition the relevance of newly defined lymphoma entities of the WHO-classification 2008, e.g. greyzone lymphomas, will be discussed for the young age group.     

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined -adrenoceptor blockade and a hyperresponsiveness of -andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to -blockers, a reduced formation of cyclic AMP in response to -adrenergic stimulation and enhanced -adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled -and -adrenergic antagonists made it possible to study - and -adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed - and -receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases.Using ¹²⁵[I]-cyanopindolol (ICYP) and ³[H]-yohimbine (HYOH) as highly specific ligands for - and -adrenoceptors, the following results were obtained: (1) Lymphocytes and platelets from control subjects and asthamatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of - and -adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. (2) In asthmatic children receiving 4×2 puffs salbutamol -adrenoceptor were down-regulated and this may mimic -adrenoceptor blockade. (3) When subjects were divided into four categories according to age (0–5, 5–10, 10–20 years, adults) the number of -adrenoceptor binding sites showed an age-dependent increase. The number and affinity of -adreneceptor binding sites on platelets was neither influenced by age nor disease.It is concluded that the - and -adrenoceptors of wheezing infants and asthmatic children at least on blood cells are normal. However the -adrenoceptors show an age-dependent maturation process, which may account for an unresponsiveness to -adrenoceptor agonists in wheezing infants.Supported by a grant from the Ministerium für Wissenschaft und Forschung, NRWPresented at the 19th Workshop for Pediatric Research, University of Göttingen, March 10–11, 1983     

小阴茎、小睾丸的诊断与治疗

小阴茎、小睾丸的病因复杂,临床诊断较为困难。下丘脑-垂体-性腺轴及雄激素合成和转化过程中任何一个环节出现异常,皆会影响阴茎和睾丸的发育。治疗应在明确诊断的基础上予以个体化方案。提倡重视小青春期内的早期诊断,以期早期治疗,使病变的危害降至最低。