辛伐他汀对肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9表达的影响

目的观察辛伐他汀对肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9表达的影响,以期探讨辛伐他汀可能的非调脂抗动脉粥样硬化的作用。方法选用体外培养的人脐静脉内皮细胞加20μg/L肿瘤坏死因子α及0.01、0.1、1.0和10μmol/L辛伐他汀共同孵育6 h1、2 h和24 h,采用免疫组织化学和逆转录聚合酶链反应分别测定基质金属蛋白酶9的免疫荧光及mRNA表达水平。结果肿瘤坏死因子α可明显诱导人脐静脉内皮细胞基质金属蛋白酶9的表达,辛伐他汀对肿瘤坏死因子α诱导的基质金属蛋白酶9 mRNA的表达有明显的抑制作用,且呈浓度依赖性和时间依赖性。结论辛伐他汀抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9的表达,可能对抗动脉粥样硬化、稳定硬化斑块、防治斑块破裂和预防急性冠状动脉综合征的发生产生有益的作用。     

骨关节炎软骨细胞和滑膜细胞金属蛋白酶活性的影响因素

目的 探讨几种细胞因子、生长因子和药物等刺激物对骨关节炎软骨细胞及滑膜细胞金属蛋白酶活性的影响。方法 骨关节炎患者的单层软骨细胞和膜细胞均以白细胞介素-1β、转化生长因子-β1、肿瘤坏死因子-α、双氯芬酸钠、多西环素和地塞松分别处理72h。应用酶谱分析细胞培养上清液中酶活性。结果 单层软骨细胞产生金属蛋白酶-9和-2,而滑膜细胞仅产生金属蛋白酶-2。白细胞介素-1β,肿瘤坏死因子-α和双氯芬酸钠均能显著增强金属蛋白酶-9活性,其中以白细胞介素-1β作用最强,与肿瘤坏死因子-α或双氯芬酸钠有协同作用。多西环素、转化生长因子-β1和地塞米松均能抑制金属蛋白酶-9和-2活性,并与白细胞介素-1β、肿瘤坏死因子-α和地塞米松均能抑制金属蛋白酶-9和-2活性,并与白细胞介素-1β、肿瘤坏死因子-α和双氯芬酸钠起拮抗作用。多西环素为最强的抑制物。结论 白细胞介素-1β和肿瘤坏死因子-α可能为破坏关节软骨的重要细胞因子,转化生长因子-β1则为保护因子,多西环素则可能成为骨关节炎的有效治疗药物。     

洛伐他汀抑制人脐静脉内皮细胞基质金属蛋白酶9表达和活性

目的观察洛伐他汀对人脐静脉内皮细胞基质金属蛋白酶9表达的影响。方法体外培养人脐静脉内皮细胞,加入20μg/L肿瘤坏死因子α诱导后,再用0.05～1.35μmol/L洛伐他汀处理0～24 h,蛋白印迹以及逆转录聚合酶链反应分别检测基质金属蛋白酶9的蛋白和mRNA表达情况,明胶酶谱法测定基质金属蛋白酶9活性。结果肿瘤坏死因子α能诱导人脐静脉内皮细胞的基质金属蛋白酶9表达和活性增强,洛伐他汀处理后,基质金属蛋白酶9的mRNA水平、蛋白量及活性均降低,且呈明显的时间和剂量依赖性,其中0.05μmol/L洛伐他汀能显著降低基质金属蛋白酶9的mRNA水平,但在蛋白水平和基质金属蛋白酶9活性上,0.05μmol/L洛伐他汀并没有表现出显著的降低效果,其余洛伐他汀各浓度均能对基质金属蛋白酶9的mRNA水平、蛋白量及活性产生显著的抑制作用,以1.35μmol/L洛伐他汀的抑制效果最显著。结论洛伐他汀能抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞基质金属蛋白酶9的表达。     

肿瘤坏死因子α介导大鼠心肌梗死后心功能变化的机制

为探讨大鼠心肌梗死后衰竭心肌肿瘤坏死因子α表达、基质金属蛋白酶活性和核因子κB活化与心肌胶原含量、心功能的相互关系,通过结扎大鼠冠状动脉前降支复制心肌梗死模型,同时设假手术组,分别在4周、8周和12周后检测血流动力学和心功能指标.同时检测左心室非梗死区心肌肿瘤坏死因子α蛋白水平、核因子κB活性、明胶分解活性和心肌胶原容积指数.结果发现,心肌梗死后心肌肿瘤坏死因子α表达显著增加,呈时间依赖性,与心功能呈负相关;心肌梗死后4周、8周和12周时心肌核因子κB活性、基质金属蛋白酶2和9活性以及胶原容积指数均呈进行性增加,而心功能逐渐恶化.以上说明,衰竭心肌核因子κB持续活化、肿瘤坏死因子α过度表达和明胶分解活性增强可能是导致心肌梗死后心室重塑和心力衰竭的重要机制之一.     

普罗布考、瑞舒伐他汀单用及合用对高血压病患者动脉粥样硬化及心功能的影响

目的 探讨普罗布考、瑞舒伐他汀单用及合用对高血压病患者动脉粥样硬化及心功能的影响.方法 入选门诊高血压病患者178例,随机分为瑞舒伐他汀治疗组(10 mg/d,睡前)、普罗布考治疗组(500 mg/d)和瑞舒伐他汀与普罗布考联合治疗组,治疗随防8个月.治疗前后行超声心动图、核素心血池检查和血清肿瘤坏死因子α、基质金属蛋白酶等检查.结果 治疗8个月后,三个治疗组与治疗前比较,总胆固醇、低密度脂蛋白胆固醇、颈动脉内膜中膜厚度和冠状动脉钙化积分均明显降低,血清肿瘤坏死因子α、基质金属蛋白酶2和基质金属蛋白酶9均明显减少;尤以联合治疗组较甚(P<0.01).联合治疗组治疗后左心室射血分数和左心室高峰充盈率明显增加.结论 普罗布考与瑞舒伐他汀合用,可进一步缓解高血压病患者的动脉粥样硬化和改善其心功能,其机制可能与降低血清肿瘤坏死因子α及基质金属蛋白酶有关.     

肿瘤坏死因子-α介导大鼠心肌梗死后心力衰竭机制的研究

目的探讨心肌梗死(心梗)后大鼠衰竭心肌肿瘤坏死因子-α(TNF-α)表达、核因子-κB(NF-κB)活性和基质金属蛋白酶(MMPs)活性与心肌胶原含量、心功能的相互关系.     

白细胞介素-1β和肿瘤坏死因子-α对血管平滑肌细胞及基质金属蛋白酶-2骨桥蛋白基因表达的影响

促炎细胞因子白细胞介素－１β和肿瘤坏死因子－α是血 滑肌细胞的强效促分裂原,为了探讨其促血管平滑肌细胞增殖是否与细胞外基质降解及粘附事成有关,本文以体外培养的血管平滑肌细胞为研究对象,应用Ｎｏｒｔｈｅｒｎ印迹及其质金属蛋白酶－２及骨桥蛋白的影响。结果发现,白细胞介素－１β和肿瘤坏死因子－α均可显著诱导基质金属蛋白本科及骨桥蛋的基因表达,血管平滑肌细胞受两种细胞因子刺激１２小时后,基质金属蛋白酶－２     

白细胞介素-1β和肿瘤坏死因子-α对血管平滑肌细胞及基质金属蛋白酶-2骨桥蛋白基因表达的影响

促炎细胞因子白细胞介素－ １β和肿瘤坏死因子－ α是血管平滑肌细胞的强效促分裂原,为了探讨其促血管平滑肌细胞增殖是否与细胞外基质降解及粘附蛋白合成有关,本文以体外培养的血管平滑肌细胞为研究对象,应用Ｎｏｒｔｈｅｒｎ 印迹及基质金属蛋白酶－ ２ 活性酶图分析方法动态观察白细胞介素－ １β、肿瘤坏死因子－ α对血管平滑肌细胞表达基质金属蛋白酶－２ 及骨桥蛋白的影响。结果发现,白细胞介素－１β和肿瘤坏死因子－ α均可显著诱导基质金属蛋白酶－ ２ 及骨桥蛋白的基因表达,血管平滑肌细胞受两种细胞因子刺激１２ ｈ 后,基质金属蛋白酶－２ 及骨桥蛋白ｍＲＮＡ表达活性最高,分别达到对照细胞的３ 倍左右和１０ 倍以上。对细胞培养基基质金属蛋白酶活性进行酶图分析的结果发现,肿瘤坏死因子－α及白细胞介素－１β作用于血管平滑肌细胞１２ 及２４ ｈ 时,基质金属蛋白酶降解明胶的活性约为对照细胞培养基的２ 倍和１．５ 倍。提示这类细胞因子可同时在多位点上对血管平滑肌细胞的迁移与增殖发挥促进作用。     

解整合素样金属蛋白酶9在食管癌中的表达

解整合素样金属蛋白酶9(ADAM-9)是属于1990年发现的锌蛋白酶总属的跨膜蛋白ADAM家族中的一员[1],至今对它的生物学功能仍不十分清楚.近来研究表明,ADAM-9与一些肿瘤的生长、转移有关,但是否与食管癌的转移有关未见报道.本研究通过在食管癌组织芯片中检测ADAM-9蛋白的表达,探讨ADAM-9在食管癌发生、发展中的作用.     

解整合素样金属蛋白酶9在食管癌中的表达

解整合素样金属蛋白酶9(ADAM-9)是属于1990年发现的锌蛋白酶总属的跨膜蛋白ADAM家族中的一员[1],至今对它的生物学功能仍不十分清楚.近来研究表明,ADAM-9与一些肿瘤的生长、转移有关,但是否与食管癌的转移有关未见报道.本研究通过在食管癌组织芯片中检测ADAM-9蛋白的表达,探讨ADAM-9在食管癌发生、发展中的作用.     

ADAM-17 is expressed in the inflammatory myopathy and is involved with interstitial lung disease

The “A disintegrin and metalloprotease” (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n?=?26), dermatomyositis (n?=?34), and clinically amyopathic dermatomyositis (n?=?10)] and healthy control (n?=?19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048?±?312 and 36?±?18 pg/ml, respectively; p?<?0.05). ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum (1465?±?562 and 1059?±?503 pg/ml, respectively; p?<?0.01). ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in inflammatory myopathy with ILD patients (n?=?46) was significantly higher than that in non-ILD patients (n?=?24) (1379?±?454 and 413?±?226 pg/ml, respectively; p?<?0.05). We found the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies especially ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.     

肿瘤坏死因子-α与脑缺血再灌注损伤

作为一种重要的炎性细胞因子,肿瘤坏死因子-α(tulllor necrosis factor-α,TNF-α)在脑缺血再灌注过程中起重要作用.探讨TNF-α,在脑缺血再灌注损伤过程中的动态变化、神经毒性作用机制以及拮抗TNF-α的治疗作用,将为脑血管病的治疗提供理论依据.     

核因子-κB、肿瘤坏死因子-α与脑梗死

核因子-κ(B(NF-κB)是广泛存在于神经元、神经胶质细胞和血管内皮细胞的一种转录因子,主要参与机体的炎症反应、细胞凋亡、免疫反应与其他应激反应,被认为是血管内皮细胞损害的始动因子.脑梗死时,肿瘤坏死因子-α等细胞因子能促进炎症级联反应,在缺血性脑损伤中同样起重要作用.     

The pro-inflammatory action of tumour necrosis factor-α in non-alcoholic steatohepatitis is independent of the NSMAF gene product

BackgroundThe role of tumour necrosis factor-α (TNF-α) in the development of non-alcoholic steatohepatitis remains unclear.AimsWe evaluated the role of TNF-α and NSMAF gene product factor associated with neutral sphingomyelinase activation, a protein adaptor of the TNF-α receptor-1, in a mouse model of non-alcoholic steatohepatitis.MethodsMice deficient either for TNF-α or factor associated with neutral sphingomyelinase activation, as well as control animals, were fed a methionine and choline-deficient diet for 5 weeks. Liver histology, serum glucose, triglycerides, cholesterol and alanine aminotransferase levels were compared between groups.ResultsWeight loss, decrease of serum triglyceride and glucose levels and increase of alanine aminotransferase levels were attenuated in TNF^?/? mice. Similarly, we found a significantly lower lobular inflammation in TNF^?/? mice. Liver expression of transforming growth factor-β, peroxisome proliferator-activated receptor-γ_{1, 2} and monocyte chemoattractant protein-1 was attenuated in TNF^?/? mice. In addition, the phosphatidylcholine/phosphatidylethanolamine liver ratio decrease was less important in TNF^?/? mice. The increase in hepatic sphingomyelin and ceramide levels was less pronounced in TNF^?/? animals.ConclusionWhereas TNF-α modulates the inflammatory process that underlies methionine and choline-deficient diet-induced non-alcoholic steatohepatitis, its effects are not mediated by factor associated with neutral sphingomyelinase activation. Whether changes in liver lipids, like phosphatidylcholine and ceramide, are causally involved in tumour necrosis factor-mediated liver inflammation remains an open issue.     

Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8(+) T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO(+) suppressive cells. This had profound effects on the balance between interleukin-17 (IL-17)-producing CD4(+) T cells and regulatory T cells. Furthermore, this caused an increase in the production of the proinflammatory cytokines IL-6 and tumor necrosis factor-α while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (ie, the TLR9 ligand cytosine-phosphate-guanosine, soluble cytotoxic T lymphocyte-associated antigen 4, or interferon γ) induced IDO-specific T cells among peripheral blood mononuclear cells from patients with cancer as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies in which IDO plays a significant regulatory role. We describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells."     

肿瘤坏死因子α诱导核转录因子κB信号通路在特发性肺纤维化中的作用机制

特发性肺纤维化（idiopathic pulmonary fibrosis,IPF）是一种由多种原因导致的、以弥漫性肺泡炎和肺泡结构紊乱、最终导致肺间质纤维化为特征的疾病.肿瘤坏死因子α（TNF-α）是一种细胞毒性因子,在肺纤维化的发病中起着关键作用.核转录因子κB（NF-κB）是一种多功能的核转录因子,近来研究表明,TNF-α可以通过激活NF-κB信号通路,参与肺纤维化的发生、发展.现对TNF-α介导NF-κB信号通路在IPF中的作用作一综述.     

兔心肌梗死后肿瘤坏死因子α信使核糖核酸表达的变化

目的研究兔心肌梗死心力衰竭后心肌肿瘤坏死因子α(TNF-α)信使核糖核酸(mRNA)表达的变化及其与心功能改变之间的相互关系。方法采用家兔在体大面积心肌梗死心力衰竭模型,为心肌梗死组。同时设假手术组,分别于术后4周、6周、10周描记左心室收缩峰压(LVSP)和左心室舒张末压,对非梗死区心肌组织采用逆转录多聚酶链反应(RT-PCR)法检测TN-FαmRNA的表达。结果心肌梗死组不同时相心肌较同期假手术组TNF-αmR-NA显著增加,有极显著差异(P<0.01),且呈时间依赖性,同LVSP呈负相关。结论心肌TNF-α基因过度表达是心肌梗死后心力衰竭发生、发展的重要机制之一。     

Side effects of TNF-α blockers in patients with psoriatic arthritis: evidences from literature studies

Psoriatic arthritis is an inflammatory rheumatic disorder, which occurs in patients with skin and/or nail psoriasis. In psoriatic arthritis, the importance of biologic mediators modulating inflammatory reaction, such as tumor necrosis factor, and the knowledge on their role in the pathogenesis of psoriatic arthritis influence the therapeutic choices. In the last years, the introduction of biologic drugs has greatly changed the treatment of psoriasis and psoriatic arthritis. In fact, tumor necrosis factor-α blockers demonstrated an effective action in the treatment of both skin and joint manifestations of psoriatic arthritis, but they have some adverse effects. The aim of this review is to revisit the literature data on adverse effects of tumor necrosis factor-α blockers in patients with psoriatic arthritis.     

肿瘤坏死因子-α与原发性高血压关系研究进展

肿瘤坏死因子-α是人体内最重要的炎症细胞因子之一,具有抗肿瘤、抗病毒、抗细菌等作用,同时对各类细胞包括内皮细胞、平滑肌细胞及心肌细胞的增殖也有调控作用。近年研究表明肿瘤坏死因子-α参与多种心脏疾病的病理生理过程。现对肿瘤坏死因子-α与高血压及其心血管重构的研究进展做一综述。