兔退变椎间盘中BNIP3的免疫组织化学研究

目的探讨兔退变椎间盘中BNIP3蛋白的表达情况。方法建立兔椎间盘穿刺退变模型,分别培养2、4、8周后对目的椎间盘进行组织HE染色、番红O染色及BNIP3免疫组织化学染色,与正常椎间盘随机对照,检测椎间盘退变程度及BNIP3蛋白表达情况。结果成功建立兔椎间盘退变模型,随椎间盘退变程度加重,BNIP3蛋白在中央髓核组织中的阳性表达逐渐增强。结论兔椎间盘退变过程中,BNIP3蛋白表达增强诱导髓核细胞死亡增加。     

Fas和Fas配体在角膜移植免疫排斥反应中的表达

目的 了解Fas和Fas配体(FasL)在发生免疫排斥的角膜植片中的表达情况，探讨其在角膜移植免疫排斥反应中的作用。方法 角膜移植术后排斥反应的患者42例，于再次行穿通性角膜移植术时取其排斥的移植片；正常角膜6例。进行免疫组织化学染色，观察正常角膜和移植片中上皮、基质和内皮层的Fas及：Fas配体的表达。结果 在6例正常角膜中，角膜上皮、内皮Fas和FasL．为阳性表达。42例移植片中，角膜上皮．Fas和FasL均有表达。有新生血管形成及免疫细胞浸润的角膜基质中，血管内皮细胞、基质细胞FasL为阳性表达，Fas在部分浸润的免疫细胞中有表达；移植片内皮细胞层广泛破坏。结论 Fas、FasL在角膜移植片中的表达，可能与角膜移植免疫排斥反应有关。     

Fas（Apo—1／CD95）及其配体在免疫病理学中的作用

Ｆａｓ系统是新近受到普遍重视的介导细胞凋亡的信号转导系统。本文主要综述了Ｆａｓ系统在某些肿瘤细胞免疫逃逸中的重要作用；Ｆａｓ系统参与淋巴细胞克隆的选择，以及参与某些自身免疫性疾病、免疫缺陷病和病毒感染性疾病病理损害的发生机理。     

Fas／FasL（配体）与免疫相关性疾病

Ｆａｓ抗原与Ｆａｓ抗原配体（ＦａｓＬ）交联后,能传导细胞凋亡信号,引起Ｆａｓ抗原表达细胞的凋亡。目前已发现,多种组织细胞能分别表达Ｆａｓ和ＦａｓＬ,有些甚至能同时表达Ｆａｓ与ＦａｓＬ在调节免疫功能、维持机体内环境的平衡方面起着重要的作用,其异常表达常与多种免疫性疾病的发生和发展有关。本文主要就近年来有关Ｆａｓ／ＦａｓＬ与免疫相关性疾病的关系作一综述。     

Fas(Apo-1/CD95)及其配体在免疫病理学中的作用

Ｆａｓ系统是新近受到普遍重视的介导细胞凋亡的信号转导系统。本文主要综述了Ｆａｓ系统在某些肿瘤细胞免疫逃逸中的重要作用；Ｆａｓ系统参与淋巴细胞克隆的选择，以及参与某些自身免疫性疾病、免疫缺陷病和病毒感染性疾病病理损害的发生机理     

椎间盘退变模型的研究进展

椎间盘退变疾病发病率越来越高,但退变的机制尚不明确.椎间盘退变模型是现今研究椎间盘退变疾病的主要方式,退变模型主要分为体内退变模型和体外退变模型两大类.两种退变模型从不同角度研究椎间盘退变的病理生理过程,为揭示退变机制及预防、治疗椎间盘退变疾病起着重要作用.本文就目前国内外关于两种不同椎间盘退变模型研究的进展作一综述.     

Fas/FasL(配体)与免疫相关性疾病

Ｆａｓ抗原与Ｆａｓ抗原配体（ＦａｓＬ）交联后,能传导细胞凋亡信号,引起Ｆａｓ抗原表达细胞的凋亡。目前已发现,多种组织细胞能分别表达Ｆａｓ和ＦａｓＬ,有些甚至能同时表达Ｆａｓ和ＦａｓＬ。Ｆａｓ与ＦａｓＬ在调节免疫功能、维持机体内环境的平衡方面起着重要的作用,其异常表达常与多种免疫性疾病的发生和发展有关。本文主要就近年来有关Ｆａｓ／ＦａｓＬ与免疫相关性疾病的关系作一综述。     

Fas／FasL与免疫性疾病

Ｆａｓ配体是一种细胞表面分子。它属于肿瘤坏死因子家族成员，并能与其受体Ｆａｓ抗原结合，从而诱导Ｆａｓ阳性的细胞凋亡，多种细胞表达Ｆａｓ，而Ｆａｓ主要由活化的Ｔ细胞表达。     

Fas／FasL与免疫性疾病

Ｆａｓ配体（ＦａｓＬ）是一种细胞表面分子，它属于肿瘤坏死因子家族成员，并能与其受体Ｆａｓ抗原（Ｆａｓ）结合，从而诱导Ｆａｓ阳性的细胞凋亡。多种细胞表达Ｆａｓ，而ＦａｓＬ主要由活化的Ｔ细胞表达。在免疫系统，Ｆａｓ／ＦａｓＬ不仅参与Ｔ细胞介导的细胞毒作用，而且具有下调免疫反应的作用。Ｆａｓ／ＦａｓＬ功能异常能导致淋巴细胞增生性疾病和促进自身免疫性疾病，而其功能过强可能导致组织损害。     

兔椎间盘退变与修复模型的研究现状*

椎间盘退变模型是研究椎间盘退变疾病的基础和关键之一。兔退变椎间盘模型具有操作简单、可重复性好等特点被国内外学者广泛应用。兔椎间盘退变模型包括体内模型、体外模型等。体内模型根据损伤类别包括:机械损伤模型、化学损伤模型、异常应力模型、脊柱不稳模型、脊柱融合模型等;体外模型包括椎间盘细胞模型、椎间盘组织模型等。本文根据近年兔腰椎间盘各种退变模型与修复的研究现状与进展作一综述。     

Expression of soluble Fas and soluble FasL in human nucleus pulposus cells

The study aimed for addressing the expression of soluble Fas (sFas) and soluble Fas Ligand (sFasL) in human nucleus pulposus (NP) and its attendant relationship with disc degeneration. Human NP samples were collected from patients with disc degeneration and cadavers as degenerate and normal groups, respectively. Subsequently, NP cells were cultured in monolayer. ELISA was performed to identify the expression levels of sFas and sFasL in the supernatant of NP cell cultures in vitro. Quantitative real-time PCR was used to detect the expression of sFas and sFasL in human NP cells in mRNA solution. The study comprised 12 degenerate and 8 normal cadaveric NP samples. The concentration value of sFas in the supernatant was significantly higher from degenerate NP than that from normal NP at each time point. In contrast, sFasL was significantly lower at each time point. Moreover, the expression of sFas and sFasL reached the peak at various early stages of cell cultures and decreased thereafter. Furthermore, the mRNA level of Fas in degenerate NP cells was significantly higher than that in normal cells; whereas FasL showed an opposite pattern. The study is the first addressing the expression of sFas and sFasL in human NP cell cultures. Moreover, the expression of sFas and sFasL varies with culture time in vitro with different levels in degenerate and normal settings. These findings indicate that sFas and sFasL might play a role in intervertebral disc degeneration.     

椎间盘退变发生机理的研究进展

生物力学因素是椎间盘退变的最重要的病理因子。异常的应力可直接引起椎间盘的破坏 ,更重要的是影响髓核、纤维环、软骨终板的细胞生物学性质 ,通过炎症机制引起椎间盘结构的退变 ;髓核自身免疫机制可能参与了髓核封闭结构破坏后的继发变过程。     

Fas (CD95)/Fas ligand interactions regulate antigen-specific,major histocompatibility complex-restricted T/B cell proliferative responses

The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed, activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM, CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein, an inhibitor of FasL-mediated cytotoxicity, to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to FasL cytotoxicity. Moreover, both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that FasL cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.     

丹红注射液对脑梗死患者血浆可溶性Fas及Fas配体浓度的影响

目的：观察丹红注射液对脑梗死患者血浆可溶性Fas及Fas配体浓度的影响,探讨丹红注射液用于脑梗死治疗的抗凋亡作用。方法：80例脑梗死患者分为对照组和治疗组,每组40例。对照组接受常规治疗,治疗组接受常规治疗加用丹红注射液治疗。脑梗死患者静脉血在人院时,人院后第1、2、3、7和14d获得,ELISA测定血浆可溶性Fas及Fas配体浓度。结果：治疗前,治疗组美国国立卫生院神经功能缺损评分与对照组比较差异无统计学意义（P〉0．05）;治疗后,治疗组美国国立卫生院神经功能缺损评分较对照组显著下降（P〈0．05）。人院时,治疗组血浆可溶性Fas及Fas配体浓度与对照组比较差异无统计学意义（P〉0．05）,人院后第1、2、3、7和14d,治疗组血浆可溶性Fas及Fas配体浓度显著低于对照组（P〈0．05）。结论：丹红注射液可能通过抑制脑梗死后神经细胞凋亡,从而达到改善神经功能的目的。     

可溶性FasL在大肠癌免疫逃逸、反击机制中的研究

目的 :探讨可溶性FasL(sFasL)在大肠癌免疫逃逸、反击机制中的作用。方法 :ELISA法检测大肠癌患者血清和结肠癌细胞株SW4 80培养上清液中sFasL的水平。透射电子显微镜、荧光显微镜和流式细胞术观察大肠癌患者术前血清和结肠癌细胞株SW4 80培养上清液诱导Jurkat细胞凋亡情况。用阻断Fas的抗体ZB4预处理Jurkat细胞后 ,观察sFasL对Jurkat细胞的特异性作用。以非洲绿猴肾细胞Vero上清液作阴性对照。结果 :大肠癌患者术前血清中sFasL的水平为 12 2 1± 1 14 μg L。术前血清中sFasL含量显著高于术后 (P <0 0 1)。分期越高、分化程度越低、有淋巴结转移、肿瘤直径 >3cm ,大肠癌术前血清中sFasL的水平越高。大肠癌细胞株SW4 80培养上清液中sFasL的含量为 (7 5 7± 0 98) μg L。透射电子显微镜观察、流式细胞术和荧光显微镜观察的结果均证实 ,大肠癌患者术前血清和SW4 80上清液sFasL均可诱导Jurkat细胞发生凋亡 ,ZB4抗体可特异性地阻断sFasL诱导的Jurkat细胞凋亡。结论 :大肠癌患者血清中和结肠癌细胞株SW4 80培养上清液中含有sFasL ,结肠癌细胞可通过sFasL诱导淋巴细胞凋亡。sFasL在大肠癌免疫逃逸、反击机制中起重要作用。     

Fas ligand exerts its pro-inflammatory effects via neutrophil recruitment but not activation

Fas ligand (FasL) expression induces apoptosis of activated T cells and has been suggested as a strategy to inhibit graft rejection. Unfortunately, the use of FasL to confer 'immune privilege' in this setting has been hampered by the finding that it may also provoke a destructive granulocytic response. While the Fas/FasL-mediated apoptotic pathways are well defined, the pro-inflammatory effects of FasL are poorly understood. Our aim in this study was to define in vitro the biological effects of FasL on neutrophil recruitment and activation. DAP-3 cells expressing human FasL on the cell membrane (mFasL) potently induced apoptosis in human neutrophils and in activated T lymphocytes. Recombinant human soluble FasL (sFasL), by contrast, was a very weak inducer of apoptosis, even at high concentrations. This latter observation suggests that cleavage of mFasL by naturally occurring matrix metalloproteinases may serve to down-regulate FasL activity in vivo. However, in the presence of a cross-linking antibody, the efficiency of apoptosis-induction by sFasL was greatly increased, suggesting that the lesser pro-apoptotic potency of sFasL reflects an inability to induce trimerization of the Fas receptor. With regard to pro-inflammatory effects, we found that sFasL is a potent neutrophil chemoattractant and, given that it induces little apoptosis, the dominance of sFasL over mFasL may mean that graft-infiltrating neutrophils will survive to mediate inflammation. Neither sFasL nor mFasL produced neutrophil activation as assessed by chemiluminescence assay. This suggests that neutrophils recruited to an inflammatory site by FasL will be activated by mechanisms other than Fas-FasL signalling.     

脲原体感染大鼠Leydig细胞时IL-6、Fas和FasL表达的变化

目的 研究Leydig细胞在抗感染中的免疫调节作用。方法 SD大鼠的睾丸经Ⅱ型胶原酶消化、过滤及Percoll分离获得高纯度、高活率的Leydig细胞。体外培养的Leydig细胞经溶脲脲原体(UU)感染后，观察其细胞培养上清液中IL-6含量(ELISA法)的变化和细胞表达Fas、FasL的变化（FACS法和RT-PCR法）。结果 UU感染可下调Leydig细胞分泌IL-6和Leydig细胞表达Fas的水平，并上调Leydig细胞表达FasL的水平，且与UU的感染剂量有关。结论 大鼠Leydig细胞在抗感染免疫中，可通过改变IL-6的分泌和Fas、FasL分子的表达而发挥免疫调节作用。     

FasL Expression on Human Nucleus Pulposus Cells Contributes to the Immune Privilege of Intervertebral Disc by Interacting with Immunocytes

The mechanisms of immune privilege in human nucleus pulposus (NP) remain unclear. Accumulating evidence indicates that Fas ligand (FasL) might play an important role in the immune privilege of the disc. We aimed for addressing the role of FasL expression in human intervertebral disc degeneration (IDD) and immune privilege in terms of the interaction between NP cells and immunocytes via the FasL-Fas machinery. We collected NP specimens from 20 patients with IDD as degenerative group and 8 normal cadaveric donors as control. FasL expression was detected by qRT-PCR, western blotting and flow cytometry (FCM). We also collected macrophages and CD8⁺ T cells from the peripheral blood of patients with IDD for co-cultures with NP cells. And macrophages and CD8⁺ T cells were harvested for apoptosis analysis by FCM after 2 days of co-cultures. We found that FasL expression in mRNA, protein and cellular resolutions demonstrated a significant decrease in degenerative group compared with normal control (p<0.05). FCM analysis found that human NP cells with increased FasL expression resulted in significantly increased apoptosis ratio of macrophages and CD8⁺ T cells. Our study demonstrated that FasL expression tends to decrease in degenerated discs and FasL plays an important role in human disc immune privilege, which might provide a novel target for the treatment strategies for IDD.