特发性肺纤维化的研究进展及其治疗

特发性肺纤维化(IPF)是一种进行性加重且目前尚无有效治疗药物的疾病,相关病因尚未明确.近期研究发现了IPF新的治疗靶点.本文综述IPF的发病机制、诊断的最新研究,以及其治疗的研究进展.     

博莱霉素诱导的肺纤维化动物模型评价及应用研究进展

特发性肺纤维化(IPF)是一种发病原因不明的严重损伤性肺部疾病,缺乏理想的治疗药物。在临床上肿瘤患者使用博莱霉素治疗后,少数患者出现肺纤维化病变。目前博莱霉素已被广泛用于制备IPF动物模型。本文对博莱霉素诱导肺纤维化动物模型的研究现状进行总结,并与临床IPF的作用机制、病理变化等进行对比评价,以期对IPF发病机制研究和药物研发有所帮助。     

自噬调节与特发性肺纤维化药物治疗研究进展

特发性肺纤维化（idiopathic pulmonary fibrosis，IPF）是一种病因复杂、与年龄相关的肺纤维化疾病，其发病过程表现出进行性与不可逆性，最终导致患者呼吸系统衰竭而死亡。近些年的研究证实自噬参与了IPF的发生发展。本文回顾总结了自噬和IPF相关的临床研究、动物和细胞模型研究以及基于自噬的药物治疗研究，希望对阐明IPF的病理机制和药物研发有所帮助。     

从指南看特发性肺纤维化治疗药物的选择

自1892年首次报道慢性间质性肺病的组织病理学以来,相关研究不断深入,其中特发性肺纤维化(IPF)发病机制的研究也取得了一定进展,但仅个别药物可能对IPF具有潜在益处.依据2011年《特发性肺纤维化诊治循证指南》,本文简要综述指南提出的4种IPF药物治疗方案的研究现状.     

细胞衰老与特发性肺纤维化药物治疗研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)是一种病因不明的破坏性肺部疾病,它的特点是细胞外基质蛋白(如胶原蛋白和纤连蛋白)在肺间质中沉积,导致呼吸衰竭。我们对IPF的病理生物学的理解仍然不完整;然而,人们普遍认为,衰老是该疾病的主要危险因素。衰老是一个复杂的过程,以不可逆的细胞周期停滞和分泌衰老相关的表型(senescence-associated secretory phenotype, SASP)为特征,导致衰老细胞不断累积和炎症发生。细胞衰老与IPF疾病进展密切相关。该文主要探讨细胞衰老的分子机制,端粒缩短、线粒体功能障碍、自噬不足及细胞凋亡抵抗等细胞衰老相关的各种诱发因素在IPF发病中的作用以及用于治疗IPF疾病的抗衰老药物,为将来治疗IPF提供理论依据和治疗方法。     

细胞衰老与特发性肺纤维化相关机制的研究进展

特发性肺纤维化(IPF)是一种随着年龄增长逐渐加重,主要表现为活动性呼吸困难,进行性加重,且不可逆的疾病。细胞衰老是衰老的标志,其定义是响应细胞损伤和压力而稳定退出细胞周期。在IPF中,导致细胞衰老的机制包括端粒功能障碍、DNA损伤、细胞衰老表型、线粒体功能障碍、炎症反应及自噬失调等,随着对衰老相关的研究进步,IPF与细胞衰老的研究也愈演愈烈,该文就这些因素与IPF的发生发展关系进行综述。     

氧化应激在特发性肺纤维化中的作用及其机制研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是以弥漫性肺泡炎和成纤维细胞病理性增生最终导致肺间质纤维化为病理特征的慢性进展性疾病。IPF发病机制尚未完全明确。成肌纤维细胞(myofibroblast)增多是目前学术界认为最为重要的IPF发生致病的主要机制。同时氧化/抗氧化失衡引起的氧化应激反应是其发病重要机制之一。纠正体内氧化/抗氧化失衡能减轻肺纤维化的程度,因此有望成为治疗特发性肺纤维化的一种新方法。该文就近年来氧化应激反应在IPF中的作用及其机制研究进展作一综述。     

肿瘤微环境中免疫细胞自身调控及中药成分对其调控的研究进展

目的 了解肿瘤微环境（tumor microenvironment, TME）中免疫细胞的调节机制、免疫治疗的新靶点以及中药成分对免疫细胞的调节作用。方法 查阅相关文献,总结TME中免疫细胞调控机制和发挥抗肿瘤免疫治疗的新靶点以及中药成分对免疫细胞的调节作用。结果 总结了肿瘤微环境中T细胞、巨噬细胞、树突状细胞在分化、发育、功能上的调控机制,归纳了抗肿瘤免疫治疗的新靶点,基于这些调控机制分析不同种类的中药成分对免疫细胞的调控作用。结论 梳理总结TME中免疫细胞的自身调控机制和中药成分对免疫细胞的调节作用,为中药抗肿瘤免疫机制的深入探索奠定基础。     

糖皮质激素治疗特发性肺纤维化急性加重的研究进展

糖皮质激素作用机制有基因组机制和非基因组机制两类,其快速而有效的抑制炎症作用主要依赖于非基因组机制。现今临床学者大多采用大剂量糖皮质激素进行冲击治疗,通过非基因组机制来使糖皮质激素快速发挥抗炎以及抗纤维化效应,但具体的“扳机点”仍处于摸索阶段。临床及病理研究提示,特发性肺纤维化急性加重( AE?IPF)的特征性病理表现为弥漫性肺泡损伤( DAD)。糖皮质激素能够抑制核因子受体和促炎细胞因子的转录以及抑制纤维细胞增生和减少胶原沉积,以致于控制 DAD。但糖皮质激素在 AE?IPF中具体剂量以及维持时间仍存在很多争议。     

肿瘤免疫逃逸的相关分子及其作用机制研究

免疫逃逸是肿瘤细胞逃避机体杀伤作用的重要途径。肿瘤细胞可通过多种途径逃避机体免疫系统的监视,如Fas/FasL(Fas Ligand)反击、诱导免疫细胞凋亡或者抑制免疫细胞增殖等。因此,该文对免疫逃逸的机制及相关分子进展进行研究,可能发现更为有效地治疗方法,缓解病人的痛苦。     

间充质干细胞治疗特发性肺纤维化药理机制研究进展

间充质干细胞（MSCs）具有多种分化能力,可以直接迁移到损伤组织中并分化为肺泡上皮细胞,还可以分泌并释放多种细胞因子和外泌体,调节炎症和免疫反应。特发性肺纤维化（IPF）是与年龄相关、发病机制尚不明确的慢性进行性肺部疾病,临床上使用的吡非尼酮和尼达尼布仅能缓解症状。MSCs在治疗IPF方面具有广阔的应用前景,就目前关于MSCs治疗特发性肺纤维化的药理机制以及该疗法所存在的局限性进行综述和探讨。     

特发性肺纤维化的组学研究进展

特发性肺纤维化(IPF)是一种原因不明的以呼吸困难和肺功能进行性恶化为特征的慢性肺纤维化性疾病,预后不良。IPF的病因尚未完全阐明,与老化、遗传、环境暴露、氧化应激和微生物-宿主防御反应有关。基因突变、转录和翻译异常、表观基因调控改变及代谢紊乱均可能影响疾病的发生和发展。近年来,采用高通量技术的组学研究从多维度揭示了IPF的发病机制,为寻找生物标志物和治疗靶点提供了新视角。本文综述了应用基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学技术阐明IPF发病机制、寻找生物标志物、提供治疗靶点的最新研究进展。     

Use of transgenic mouse models to understand the origins of familial pulmonary fibrosis

Pulmonary fibrosis is an unremitting degenerative lung disease that has an associated high mortality. The major pathological features include the growth of fibroblasts, emergence of myofibroblasts and their production of extracellular matrix that distorts the peripheral lung tissue and impairs respiratory function. Efforts to pharmacologically reduce inflammation, inhibit fibroblast growth, or matrix synthesis have not been successful in ameliorating disease. Genetic mutations associated with rare hereditary forms of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) link definitive causes to this enigmatic group of diseases. The generation of mouse models with similar genetic lesions or deficiencies is providing insight into the mechanisms that lead to fibrosis. Mutations that alter components of pulmonary surfactant or surfactant homeostasis have been associated with specific forms of ILD and/or IPF. This small but growing collection of IPF related surfactant dysfunction mutations implicate respiratory epithelial cell injury as an early event in the molecular pathogenesis and progression of fibrosis. Determining the mechanisms for genetically defined examples of IPF should be informative for investigating the larger segment of IPF where the underlying cause remains obscure.     

特发性肺纤维化治疗药物的研究进展

特发性肺纤维化(IPF)是一种不可逆、进展性、致死性的慢性肺纤维化疾病,其进展较快,存活率较低,缺乏有效诊疗手段和治疗药物。近年来随着对其发病机制的了解,IPF治疗药物的开发也取得了一定进展。全球新批准并上市的治疗药物有吡非尼酮和尼达尼布,处于研发I、II期的有10多种,另外也有一些曾经有希望但已经不推荐用于IPF治疗的药物。     

New Insights into the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis: A Potential Role for Stem Cells in the Lung Parenchyma and Implications for Therapy

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood. This highly lethal lung disorder continues to pose major clinical challenges since an effective therapeutic regimen has yet to be identified and developed. For example, a treatment modality has been based on the assumption that IPF is a chronic inflammatory disease, yet most available anti-inflammatory drugs are not effective in treating it. Hence researchers are now focusing on understanding alternative underlying mechanisms involved in the pathogenesis of IPF in the hope of discovering potentially new pharmaceutical targets. This paper will focus on lung tissue repair, regeneration, remodeling, and cell types that may be important to consider in therapeutic interventions and includes a more detailed discussion of the potential targets of current therapeutic attack in pulmonary fibrosis. The discovery that adult bone marrow stem cells can contribute to the formation of differentiated cell types in other tissues, especially after injury, implies that they have the potential to participate in tissue remodeling, and perhaps regeneration. The current promise of the use of adult stem cells for tissue regeneration, and the belief that once irreversibly damaged tissue could be restored to a normal functional capacity using stem cell-based therapy, suggests a novel approach for treatment of diverse chronic diseases. However this optimism is tempered by current evidence that the pathogenesis of pulmonary fibrosis may involve the recruitment of bone marrow-derived fibroblasts, which are the key contributors to the pathogenesis of this chronic progressive disorder. Nevertheless, stem cell-related therapies are widely viewed as promising treatment options for patients suffering from various types of pulmonary diseases. Gender mismatched bone marrow or lung transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary diseases. Understanding the mechanism of recruitment of stem cells to sites of injury, and their involvement in tissue repair, regeneration, and remodeling may offer a novel therapeutic target for developing more effective treatments against this fatal disorder. This article reviews the new concepts in the pathogenesis, current and future treatment options of pulmonary fibrosis, and the recent advances regarding the roles of stem cells in lung tissue repair, regeneration, and remodeling.     

Targeting the endothelin pathway in the idiopathic pulmonary fibrosis: the role of bosentan

Background: Idiopathic pulmonary fibrosis (IPF) is a rapidly lethal disease characterized by anarchic, progressive fibrosis. Pulmonary fibrosis is the result of interactions between many effector cells and cytokines and better understanding of this can help with identification of novel therapeutic targets. Objective: To evaluate the role of the endothelin-1 (ET-1) pathway in IPF pathogenesis and the effects of therapeutic targeting with bosentan, an ET-1 antagonist. Methods: Data on ET-1's pathogenic involvement in IPF and the preclinical and clinical data on bosentan in this context are discussed and analyzed. A parallel overview of existing and upcoming therapies for IPF is presented. Conclusions: Bosentan is a promising antifibrotic therapy for IPF and clinical data on its long-term efficacy support its use.     

Determination of sunscreen immune protection factors using human dendritic cell suspensions.

In a previous study, we have used UVB-irradiated human skin explants and the allostimulatory function of Langerhans cells (LC) to determine immune protection factors (IPF) for sunscreens. We sought here to simplify the model by using either human enriched LC suspensions or in vitro generated dendritic cells from human monocytes (MoDC). LC or MoDC suspensions were irradiated with increasing doses of UVB through a piece of translucent strip recovered or not with the sunscreens. The allostimulatory function of the cells was then analysed in a mixed lymphocyte reaction and the UVB dose providing 50% immunosuppression (D50%) was determined graphically. IPF were determined by the ratio of the D50% value in the presence of sunscreen to that of the vehicle alone. In either experimental conditions, the D50% in the presence of sunscreens was significantly higher (p < 0.01) than that obtained with the vehicle, demonstrating the sunscreen immunoprotective effect. IPF values obtained with either DC suspensions were very similar and quite comparable to those previously obtained in the skin explant model. Thus, the present in vitro model provides easy tools to determine a new important biological parameter for sunscreens, i.e. immune protection.