病毒感染与自身免疫病

自身免疫是机体失去对自身抗原的免疫耐受或免疫无反应性,其病因与发病机制十分复杂。已证明某些病毒感染与 些自身免疫病密切相关,并发现病毒与宿主细胞的某些基因或其蛋白了之间存在着结构类似性,因而可发生交叉免疫反应性。这种分子模拟假说得到转基因动物实验的支持。它对于进一步深入研究自身免疫病的病因,发病机制以及治疗和预防具有重要意义。     

抑郁症的成因及其新药治疗研究进展

抑郁症是一种发病率高、危害大的精神疾病,且发病的人群正在急剧增加。抑郁症的成因复杂,其病因机制尚不十分清楚。目前研究的病因主要包括神经递质受体异常、神经退化及内分泌、炎症细胞因子、表观遗传调节和大脑衍生神经营养因子等。随着新病因的揭开,抑郁症治疗的新药及其作用机理研究也取得了较大的进展。研发的新药主要包括:选择性5-羟色胺(5-HT)、去甲肾上腺素(NE)再摄取抑制剂、选择性NE再摄取抑制剂、肾上腺素能和特异性5-HT抗抑郁药、以及新药氯胺酮。本文就抑郁症发病的成因及主要的新药治疗策略进行了综述,为揭示抑郁症致病机制及其新药研发提供了理论依据。     

念珠菌性外阴阴道炎发病机制研究进展

念珠菌性外阴阴道炎是一种常见的妇女感染性疾病,该病发病机制尚未完全明确,其发病与多种因素有关,但主要归因于致病菌与宿主两方面因素。近20a的动物及临床研究显示适应性免疫涉及的几种免疫调节机制可能不是主要的保护性机制,天然免疫被认为是黏膜念珠菌感染的主要宿主防御机制;而念珠菌毒力因子的变化对于该病的发生也有重要作用。     

病原微生物相关自身免疫性甲状腺疾病的研究进展

自身免疫性甲状腺疾病(autoimmune thyroid disease, AITD)患病率逐年在增高,已成为内分泌系统最常见的病种之一,但其病因和发病机制尚不十分清楚,目前普遍认为其发生是遗传、环境、感染、精神等因素共同作用的结果。其中,病原微生物感染被认为是引发AITD的重要因素之一。这些病原微生物入侵人体后,在发生感染的同时,能激发人体免疫系统产生一系列免疫应答,诱发甲状腺的自身免疫反应。现就病原微生物对AITD的影响及特定病原微生物在AITD中的发病机制作一概述,为甲状腺疾病的预防、诊断和治疗等提供新的方向和依据。     

益生菌防治过敏性疾病的进展和展望

过敏是一种病理性的免疫反应。随着全球患病率逐年上升,它已成为困扰人类健康的常见疾病。目前针对过敏性疾病的疗法大都收效甚微。研究证实,益生菌可以刺激免疫细胞的免疫调节特性,维持免疫内环境平衡,调节胃肠道生态系统,是潜在的防治过敏性疾病的有效疗法。改变抗原提呈细胞的功能或调节Th1/Th2平衡是益生菌抗过敏的基本作用机制。目前益生菌防治过敏性疾病已经成为国内外研究的热点,未来有望利用益生菌实现过敏性疾病的个性化与精准化治疗。本文就益生菌防治过敏性疾病的最新进展以及该领域前沿作一综述,期望有助于我国益生菌治疗和预防过敏性疾病的普及和研究。     

卵巢早衰候选基因的突变研究进展

卵巢早衰病因复杂, 多数病例病因不明。在已知的病因中, 遗传因素非常重要。卵巢早衰不但可导致不孕症, 患者的低雌激素水平还增加了患骨质疏松症和冠心病的危险。目前临床上的主要治疗措施包括激素替代治疗和供卵治疗不孕症等, 但效果都不理想。鉴定卵巢早衰的致病基因是从根本上治疗和预防该病的基础。目前已发现在X染色体上和常染色体上多个基因与之相关, 文章综述了近年来对卵巢早衰候选基因的突变分析情况, 旨在从分子水平分析研究卵巢早衰的发病机制提供基础。     

非动脉炎性前部缺血性视神经病变诊疗策略及其脉络膜厚度

非动脉炎性前部缺血性视神经病变(nonarteritic anterior ischemic optic neuropathy,NAION),是一种比较常见视神经疾病,病因、发病机制复杂,治疗效果有限,多年来一直是眼科医生为取得突破性进展而不懈努力的方向。近年来,随着频域相干光断层深度增强成像(enhanced depth imaging spectral-domain optical coherence tomography,EDI-OCT)越来越广泛的应用,为NAION发病机制的研究提供了新的思路:鉴于前部视神经的血供主要来源于睫状后小血管,而这些小血管又构成了脉络膜的主要部分,因此应用EDI-OCT对脉络膜厚度的研究或将为该病发病机制的阐释、治疗效果的评估及预后的随访提供更加便捷的途径。在此,对近年来NAION病因、发病机制、诊断、治疗以及其脉络膜厚度的研究进展进行综述。     

糖尿病肾病啮齿动物模型研究进展*

糖尿病肾病(Diabetic nephropathy,DN),是糖尿病微血管病变中常见的并发症,也是发展为终末期肾病(End stage renaldisease,ESRD)的主要原因之一,其病因与发病机制非常复杂,至今尚未完全阐明。理想的动物模型研究对于探索DN的病因、发病机制,发病早期作出诊断、发现临床相关治疗靶点并探索新的治疗方法,评价干预措施等方面有着不可替代的作用。本文现就目前国内外常用的DN啮齿动物模型展开综述,探讨不同DN啮齿动物模型的特点和应用范围。     

帕金森病研究进展

帕金森病(Parkinson’s disease,PD)是一种多发于中老年期的,以黑质多巴胺能神经元选择性变性为主要病理改变的神经系统退行性疾病。目前,对该病的病因和发病机制还不清楚,尚未建立特异的、灵敏的预警和早期诊断体系以及确切有效的神经保护和治疗的方法。PD的发病与人口老龄化密切相关,随着我国老龄化社会的到来,PD发病率不断增加,给社会和经济都带来严重的危害,因此,越来越受到国家和政府的关注。本世纪以来,科技部先后设立"神经变性病的机制和防治的基础研究"以及"帕金森病发病机制及防治策略的研究"两个973计划项目,以求系统、深入研究PD的病因,神经元选择性、进行性变性死亡的关键机制以及寻找能延缓或阻断疾病的药物等防治新策略,期望推动我国的PD研究,为建立PD防治的新理论、新策略和新技术等奠定扎实的基础。对这两个973项目PD研究团队的主要原创性工作进行综述。     

脑胶质瘤动物模型的研究及应用进展

脑胶质瘤约占中枢神经肿瘤的一半,临床治疗效果差。尤其是胶质母细胞瘤,其恶性程度极高,预后性差,是威胁人类健康的主要恶性肿瘤之一,因此,选择一种有效的动物模型是研究脑胶质瘤发病机制及其治疗方法的关键。随着分子生物学、遗传学的发展,尤其是转基因小鼠,以及其他越来越多模式生物的出现,目前已建立了多种脑胶质瘤动物模型。该文将对目前所建立的各种脑胶质瘤动物模型予以综述。     

Chemokine Receptors CCR6 and CXCR3 Are Necessary for CD4+ T Cell Mediated Ocular Surface Disease in Experimental Dry Eye Disease

CD4⁺ T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4⁺ T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN-γ and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4⁺ T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4⁺ T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease.     

翼状胬肉的发病机制及治疗的现状与进展

翼状胬肉具有较高的发病率,作为眼表疾病之一,如不给予及时有效的治疗会对患者的外貌产生影响,同时造成视力受损。迄今为止,翼状胬肉的具体发病机制尚未完全明确,且治疗方式复杂多样。为了有效提高翼状胬肉的治疗效果,降低复发率,研究学者与临床医师开始针对翼状胬肉的发病机制开展了大量研究,同时对临床治疗方式也进行了诸多改进,且将新型的药物以及医疗器械应用于临床治疗中,为翼状胬肉的防治提供了新的思路。但是其确切的发病机制还有待进一步研究,本文在角膜缘干细胞缺乏、炎性细胞因子、病毒感染细胞凋亡、转化生长因子-β、神经生长因子(NGF)以及血管内皮细胞生长因子(VEGF)方面的研究进行了综述。     

杞菊地黄汤联合玻璃酸钠滴眼液对肝肾阴虚型干眼症患者眼表功能和泪液MMP-2、MMP-9水平的影响

摘要 目的：观察杞菊地黄汤联合玻璃酸钠滴眼液治疗肝肾阴虚型干眼症的疗效及对眼表功能和泪液基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）的影响。方法：病例来源于2018年6月~2021年3月期间就诊于湖南省直中医医院眼科门诊的干眼症患者,共98例。采用随机数字表法分为对照组和实验组,两组均49例。对照组给予玻璃酸钠滴眼液治疗,实验组在对照组基础上接受杞菊地黄汤治疗,两组均治疗4周。对比两组疗效、中医证候积分、眼表功能和泪液MMP-2、MMP-9水平变化,观察两组治疗期间不良反应发生率。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组治疗4周后眼部干涩不爽、畏光、双目频眨、口干少津、白眼泛红、舌红、苔薄、脉细证候积分均低于对照组（P<0.05）。实验组治疗4周后角膜荧光素染色（FL）评分低于对照组,泪膜破裂时间（BUT）、泪液分泌试验（SIT）水平高于对照组（P<0.05）。实验组治疗4周后泪液MMP-2、MMP-9水平低于对照组（P<0.05）。两组间不良反应发生率无统计学差异（P＞0.05）。结论：杞菊地黄汤联合玻璃酸钠滴眼液治疗肝肾阴虚型干眼症,可促进患者症状缓解,改善眼表功能,降低泪液MMP-2、MMP-9水平,安全可靠。     

Lipidomic analysis of epithelial corneal cells following hyperosmolarity and benzalkonium chloride exposure: New insights in dry eye disease

Dry eye disease (DED) is a multifactorial chronic inflammatory disease of the ocular surface characterized by tear film instability, hyperosmolarity, cell damage and inflammation. Hyperosmolarity is strongly established as the core mechanism of the DED. Benzalkonium chloride (BAK) - a quaternary ammonium salt commonly used in eye drops for its microbicidal properties - is well known to favor the onset of DED. Currently, little data are available regarding lipid metabolism alteration in ocular surface epithelial cells in the course of DED. Our aim was to explore the effects of benzalkonium chloride or hyperosmolarity exposure on the human corneal epithelial (HCE) cell lipidome, two different conditions used as in vitro models of DED. For this purpose, we performed a lipidomic analysis using UPLC-HRMS-ESI+/−. Our results demonstrated that BAK or hyperosmolarity induced important modifications in HCE lipidome including major changes in sphingolipids, glycerolipids and glycerophospholipids. For both exposures, an increase in ceramide was especially exhibited. Hyperosmolarity specifically induced triglyceride accumulation resulting in lipid droplet formation. Conversely, BAK induced an increase in lysophospholipids and a decrease in phospholipids. This lipidomic study highlights the lipid changes involved in inflammatory responses following BAK or hyperosmolarity exposures. Thereby, lipid research appears of great interest, as it could lead to the discovery of new biomarkers and therapeutic targets for the diagnosis and treatment of dry eye disease.     

Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis

As specialized sentinels between the innate and adaptive immune response, APCs are essential for activation of Ag-specific lymphocytes, pathogen clearance, and generation of immunological memory. The process is tightly regulated; however, excessive or atypical stimuli may ignite activation of APCs in a way that allows self-Ag presentation to autoreactive T cells in the context of the necessary costimulatory signals, ultimately resulting in autoimmunity. Studies in both animal models and patients suggest that dry eye is a chronic CD4(+) T cell-mediated ocular surface autoimmune-based inflammatory disease. Using a desiccating stress-induced mouse model of dry eye, we establish the fundamental role of APCs for both the generation and maintenance of ocular-specific autoreactive CD4(+) T cells. Subconjunctival administration of liposome-encapsulated clodronate efficiently diminished resident ocular surface APCs, inhibited the generation of autoreactive CD4(+) T cells, and blocked their ability to cause disease. APC-dependent CD4(+) T cell activation required intact draining cervical lymph nodes, as cervical lymphadenectomy also inhibited CD4(+) T cell-mediated dry eye disease. In addition, local depletion of peripheral conjunctival APCs blocked the ability of dry eye-specific CD4(+) T cells to accumulate within the ocular surface tissues, suggesting that fully primed and targeted dry eye-specific CD4(+) T cells require secondary activation by resident ocular surface APCs for maintenance and effector function. These data demonstrate that APCs are necessary for the initiation and development of experimental dry eye and support the standing hypothesis that dry eye is a self-Ag-driven autoimmune disease.     

玻璃酸钠联合重组牛碱性成纤维细胞生长因子对糖尿病性白内障超声乳化术后泪膜稳定性的影响

目的:探讨玻璃酸钠联合重组牛碱性成纤维细胞生长因子(b FGF)对糖尿病性白内障超声乳化术后泪膜稳定性的影响。方法:选取2015年1月到2017年1月期间在我院接受治疗的150例糖尿病性白内障患者,根据随机数字表法分为对照组和研究组,各75例。两组均进行常规治疗,在常规治疗的基础上对照组采用玻璃酸钠滴眼液进行治疗,研究组在对照组的基础上加用bFGF眼用凝胶进行治疗,两组均治疗1个月。比较两组术前、术后1周、术后1个月的泪膜破裂时间(BUT)、基础泪液分泌试验(SIt)值、角膜荧光素染色(FL)评分、干眼症状评分和眼表疾病指数(OSDI)评分,并比较两组术前、术后1个月的最佳矫正视力。结果:术后1周,两组患者的BUT明显低于术前和术后1个月,且研究组的BUT高于对照组(P0.05);随时间推移两组患者的OSDI评分持续降低(P0.05),术后1周,两组患者干眼症状评分、SIt值、FL评分明显高于术前和术后1个月,且研究组的OSDI评分、干眼症状评分、SIt值、FL评分均低于对照组(P0.05)。术后1个月两组患者的最佳矫正视力均明显上升,且研究组明显高于对照组(P0.05)。结论:玻璃酸钠联合bFGF能有效提升糖尿病性白内障患者在超声乳化术后泪膜稳定性,利于患者术后视力的恢复,值得临床推广应用。     

Selenium Compound Protects Corneal Epithelium against Oxidative Stress

The ocular surface is strongly affected by oxidative stress, and anti-oxidative systems are maintained in corneal epithelial cells and tear fluid. Dry eye is recognized as an oxidative stress-induced disease. Selenium compound eye drops are expected to be a candidate for the treatment of dry eye. We estimated the efficacy of several selenium compounds in the treatment of dry eye using a dry eye rat model. All of the studied selenium compounds were uptaken into corneal epithelial cells in vitro. However, when the selenium compounds were administered as eye drops in the dry eye rat model, most of the selenium compounds did not show effectiveness except for Se-lactoferrin. Se-lactoferrin is a lactoferrin that we prepared that binds selenium instead of iron. Se-lactoferrin eye drops suppressed the up-regulated expression of heme oxygenase-1, cyclooxygenase-2, matrix metallopeptidase-9, and interleukin-6 and also suppressed 8-OHdG production in the cornea induced by surgical removal of the lacrimal glands. Compared with Se-lactoferrin, apolactoferrin eye drops weakly improved dry eye in high dose. The effect of Se-lactoferrin eye drops on dry eye is possibly due to the effect of selenium and also the effect of apolactoferrin. Se-lactoferrin is a candidate for the treatment of dry eye via regulation of oxidative stress in the corneal epithelium.     

In-depth analysis of the human tear proteome

The tears, a critical body fluid of the surface of the eye, contain an unknown number of molecules including proteins/peptides, lipids, small molecule metabolites, and electrolytes. There have been continued efforts for exploring the human tear proteome to develop biomarkers of disease. In this study, we used the high speed TripleTOF 5600 system as the platform to analyze the human tear proteome from healthy subjects (3 females and 1 male, average age: 36±14). We have identified 1543 proteins in the tears with less than 1% false discovery rate, which represents the largest number of human tear proteins reported to date. The data set was analyzed for gene ontology (GO) and compared with the human plasma proteome, NEIBank lacrimal gland gene dataset and NEIBank cornea gene dataset. This comprehensive tear protein list may serve as a reference list of human tear proteome for biomarker research of ocular diseases or establishment of MRM (Multiple Reaction Monitoring) assays for targeted analysis. Tear fluid is a useful and an accessible source not only for evaluating ocular surface tissues (cornea and conjunctiva), inflammation, lacrimal gland function and a number of disease conditions, such as dry eye as well as response to treatment.     

与眼部疾病相关的长链非编码RNA的研究进展

长链非编码RNA(long non-coding RNA,LncRNA)是一类长度大于200个核苷酸不具备编码蛋白质功能的转录子,在表观遗传、转录或转录后水平调节基因的表达,维持细胞稳态。研究表明多种LncRNA的表达失衡在肿瘤细胞的增殖、转移、干细胞的全能性、免疫细胞的发育及应答过程中发挥重要。新近的研究显示许多LncRNAs特异表达与眼部疾病发生密切相关。本文主要对目前报道的与眼部常见疾病如翼状胬肉、白内障、青光眼、糖尿病视网膜病变、眼部肿瘤等差异表达LncRNAs的功能和作用机制进行了综述,以期为LncRNAs作为眼部疾病的生物学标记和潜在治疗靶点的的应用提供参考资料。     

与眼部疾病相关的长链非编码RNA的研究进展

长链非编码RNA(long non-coding RNA,LncRNA)是一类长度大于200个核苷酸不具备编码蛋白质功能的转录子,在表观遗传、转录或转录后水平调节基因的表达,维持细胞稳态。研究表明多种LncRNA的表达失衡在肿瘤细胞的增殖、转移、干细胞的全能性、免疫细胞的发育及应答过程中发挥重要。新近的研究显示许多LncRNAs特异表达与眼部疾病发生密切相关。本文主要对目前报道的与眼部常见疾病如翼状胬肉、白内障、青光眼、糖尿病视网膜病变、眼部肿瘤等差异表达LncRNAs的功能和作用机制进行了综述,以期为LncRNAs作为眼部疾病的生物学标记和潜在治疗靶点的的应用提供参考资料。