单核细胞趋化蛋白-1、癌胚抗原和C-反应蛋白在平阳霉素胸膜固定术中的变化及意义

目的 观察胸膜腔内注射平阳霉素(PYM)后胸腔积液(胸水)中单核细胞趋化蛋白-1(MCP-1)-1、癌胚抗原(CEA)和C-反应蛋白(CRP)水平的变化,探讨PYM胸膜固定术的机制.方法 2009年10月至2010年8月对31例恶性胸腔积液患者胸膜腔内注射PYM,检测注药前及注药后6 h、24 h、48 h胸水中MCP...     

氯沙坦对血管平滑肌细胞内单核细胞趋化因子-1表达的影响

为了探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对血管平滑肌细胞内单核细胞趋化蛋白 1表达的影响 ,以培养幼兔主动脉平滑肌细胞为研究对象 ,分别给予不同浓度血管紧张素Ⅱ和 或血管紧张素Ⅱ受体拮抗剂氯沙坦 ,采用免疫组织化学、原位杂交与酶联免疫吸附技术检测不同处理组平滑肌细胞内单核细胞趋化蛋白 1蛋白及其mR NA表达和平滑肌细胞培养介质中单核细胞趋化蛋白 1含量的变化。结果发现 ,10 - 6 ～ 10 - 1 0 mol L血管紧张素Ⅱ呈剂量依赖性地增加平滑肌细胞内单核细胞趋化蛋白 1蛋白及其mRNA表达水平 ,增高培养介质中单核细胞趋化蛋白 1蛋白含量 (P均 <0 .0 0 1)。 10 - 5 ～ 10 - 7mol L氯沙坦预处理使血管紧张素Ⅱ刺激的平滑肌细胞内单核细胞趋化蛋白 1蛋白及其mRNA表达水平及培养介质中单核细胞趋化蛋白 1蛋白含量明显减低 (P均 <0 .0 0 1)。以上结果提示 ,氯沙坦可拮抗血管紧张素Ⅱ所致的平滑肌细胞内单核细胞趋化蛋白 1的表达与分泌 ,这可能有助于减轻或防治某些病理状态下血管平滑肌细胞的增殖与迁移。     

单核细胞趋化蛋白-1及受体在血管紧张素Ⅱ诱导的血管病变中的作用

在血管紧张素Ⅱ诱导的血管病变中,单核细胞趋化蛋白-1是最重要的化学趋化因子之一。血管紧张素Ⅱ通过一系列分子途径诱导单核细胞趋化蛋白-1的产生,并与其受体CCR2结合,进而引起或加速一系列血管疾病的进程。现就单核细胞趋化蛋白-1及受体CCR2在血管病变中的作用及血管紧张素Ⅱ诱导单核细胞趋化蛋白-1表达的分子途径作一综述。     

血管内皮生长因子与恶性胸腔积液的关系

临床上恶性胸腔积液是肿瘤常见的并发症,多项研究表明血管内皮生长因子(vascular endothelial growth factor,VEGF)在恶性胸腔积液中明显升高,其调控肿瘤的生长、血管的密度和渗透性及肿瘤的转移,从而影响恶性胸腔积液的产生.VEGF通过不同机制调控血管的通透性,还与炎症、凝血等途径相互作用.VEGF联合其他指标可作为辅助诊断及鉴别诊断的依据,同时部分VEGF/VEGFR对恶性胸腔积液有明确疗效.     

肿瘤相关抗原RCAS1与恶性胸腔积液

RCAS1可促进肿瘤细胞生长、转移及逃避机体免疫监测,诱导外周免疫细胞生长抑制、凋亡,肿瘤新生血管形成及结缔组织重塑.本文从恶性胸腔积液的发病机制着手,重点阐述RCAS1在恶性胸腔积液发生、发展中的作用.     

肿瘤坏死因子在恶性胸水局部治疗中的应用及进展

<正>恶性胸腔积液(malignant pleural effusion,MPE)是恶性肿瘤的常见并发症,多见于晚期肺癌、乳腺癌和淋巴瘤患者,约占68%,少数由卵巢癌、胃癌、子宫颈癌和肉瘤等引起。肿瘤患者出现恶性胸腔积液提示患者预后不良,患者生存期一般小于6个月[1-4]。恶性胸腔积液可引起患者出现压迫性肺不张、限制性通气功能障碍、纵隔移位和回心血流量减少,严重影响患者的呼吸和循环功能,所以有效控制恶性胸腔积液对提高晚期肿瘤患者生存期和生存质量有着非常重要的临床意义。肿瘤坏死因子(tumor necrosis factor,TNF)是由巨噬细胞、单核细胞等细胞分泌的细胞因子,是目前认为最强的杀     

氯沙坦通过下调单核细胞趋化蛋白1受体表达抑制单核细胞活化

目的探讨血管紧张素Ⅱ对单核细胞趋化蛋白1受体CCR2表达的影响及氯沙坦的干预作用。方法人单核细胞株与血管紧张素Ⅱ(10-7mol/L)孵育,加或不加氯沙坦(10-7、10-6和10-5mol/L),检测上清液中单核细胞趋化蛋白1水平、单核和内皮细胞粘附情况以及CCR2mRNA的表达。结果与对照组比较,血管紧张素Ⅱ明显增加单核细胞培养上清液中单核细胞趋化蛋白1水平(26.46±3.58ng/L比10.56±2.34ng/L,P<0.01),增加单核内皮细胞间粘附(596±27比268±16,P<0.01)。血管紧张素Ⅱ刺激细胞后明显上调CCR2mRNA表达,氯沙坦能显著抑制血管紧张素Ⅱ的作用,降低单核细胞趋化蛋白1的水平,减少单核内皮细胞间粘附,下调CCR2 mRNA表达。结论氯沙坦通过下调单核细胞趋化蛋白1受体CCR2基因表达抑制单核细胞活化。     

睾酮通过芳香化酶途径抑制人血管内皮细胞单核细胞趋化蛋白1的基因表达

目的 探讨睾酮对脐静脉内皮细胞生成单核细胞趋化蛋白1的影响与机制,分析睾酮与内皮细胞功能及动脉粥样硬化的关系.方法 脂多糖刺激体外培养的脐静脉内皮细胞,培养液中分别加入不同浓度睾酮(3×10-10、3×10-9、3×10-8、3×10-6 mol/L和3×10-4 mol/L),ELISA实验方法检测细胞上清液单核细胞趋化蛋白1蛋白含量,RT-PCR方法检测单核细胞趋化蛋白1 mRNA相对水平.培养液中加入雄激素受体拮抗剂或芳香化酶抑制剂,重复上述实验.结果 与空白对照组(374.16±10.2)比较,3×10-10 mol/L睾酮组上清液单核细胞趋化蛋白1蛋白含量明显增}Jn(424.50±11.3,P＜0.05),随着睾酮浓度增加,单核细胞趋化蛋白1逐渐减少,3×10-5 mol/L组差异具有统计学意义(292.29±12.6,P＜0.01).与对照组比较,3×10-9,3×10-6,3×10-5 mol/L组单核细胞趋化蛋白1mRNA水平明显降低.雄激素受体拮抗剂可逆转3×10-10mol/L睾酮对单核细胞趋化蛋白1对蛋白生成的影响,芳香化酶抑制剂可削弱睾酮对内皮细胞单核细胞趋化蛋白1基因表达与蛋白合成的抑制作用.结论 睾酮浓度降低,可促进血管内皮细胞发生炎症反应;睾酮达到生理浓度抑制内皮细胞发生炎症反应,这种作用是睾酮通过细胞内芳香化酶转化为雌激素实现的.     

血管内皮生长因子联合基质金属蛋白酶-9对老年人恶性胸腔积液的诊断价值

血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)均与肿瘤转移有关.有研究显示,VEGF在癌性胸腔积液中高于结核性胸腔积液[1],但对VEGF在胸腔积液中的诊断价值还有争论[2].MMP-9在不同病因的胸腔积液中变异较大[3-5].本研究旨在探讨VEGF联合MMP-9在恶性胸腔积液临床诊断中的价值.     

肿瘤标志物在肺癌引起胸腔积液诊断中的应用进展

胸腔积液是一个常见的临床表现.其良恶性的判断与治疗、预后密切相关.许多方法和指标都曾尝试用于恶性胸腔积液的诊断,各有利弊.随着分子生物学和实验技术的迅速发展,新的诊断指标和检测方法不断涌现.肿瘤标志物包括肿瘤相关抗原,肿瘤相关蛋白等,对于肺癌引起的胸腔积液的鉴别诊断具有重要的意义.     

Decreased Expression of Monocyte Chemoattractant Protein-1 Predicts Poor Prognosis Following Curative Resection of Colorectal Cancer

Purpose  The significance of monocyte chemoattractant protein-1 in colorectal cancer is not well understood. The aim of this study was to investigate the significance of monocyte chemoattractant protein-1 expression in colorectal cancer patients undergoing potentially curative surgery. Methods  We studied 101 colorectal cancer patients who underwent potentially curative surgery. The concentration of monocyte chemoattractant protein-1 in the tumor and normal mucosa were measured. The expression of monocyte chemoattractant protein-1 was also evaluated immunohistochemically. Results  The tissue concentration of monocyte chemoattractant protein-1 in the tumor was significantly higher than that in the normal mucosa. The decreased monocyte chemoattractant protein-1 cancer/normal ratio was associated with lymph node involvement and could predict poor prognosis. On univariate analysis, the decreased monocyte chemoattractant protein-1 ratio, carcinoembryonic antigen levels, and serosal invasion were the significant factors for poor prognosis. Multivariate analysis showed that monocyte chemoattractant protein-1 ratio was the only independent risk factor predictive of a poor prognosis. Immunohistochemically, monocyte chemoattractant protein-1 was expressed in the cytoplasm. Conclusion  The decreased monocyte chemoattractant protein-1 ratio was an independent factor predicting poor prognosis in patients undergoing potentially curative surgery. Monocyte chemoattractant protein-1 deficiency may present a new therapeutic approach for colorectal cancer.     

高同型半胱氨酸血症大鼠冠状动脉内皮细胞单核细胞趋化蛋白1的表达

目的观察高同型半胱氨酸血症对大鼠冠状动脉内皮细胞表达单核细胞趋化蛋白1的影响,以明了冠状动脉粥样硬化性心脏病的发病机制。方法24只大鼠随机分成正常饮食对照组、高蛋氨酸饮食组、高蛋氨酸 叶酸饮食组、高半胱氨酸饮食组。每组6只,分别给予普通饲料;普通饲料加1.7%蛋氨酸;普通饲料加1.7%蛋氨酸和0.006%叶酸;普通饲料加1.2%半胱氨酸。饲养6周,采用高效液相色谱荧光检测法测定血浆总同型半胱氨酸浓度,免疫组织化学染色法检测大鼠冠状动脉左主干和左前降支内皮细胞单核细胞趋化蛋白1的表达。结果喂以高蛋氨酸饲料6周,可诱导大鼠高同型半胱氨酸血症。与正常饮食对照组比较,高蛋氨酸饮食组大鼠血浆总同型半胱氨酸浓度显著升高(P<0.01),冠状动脉内皮单核细胞趋化蛋白1的表达水平明显增强;高蛋氨酸 叶酸饮食组大鼠血浆总同型半胱氨酸水平较高蛋氨酸饮食组显著降低(P<0.01),其冠状动脉内皮单核细胞趋化蛋白1的表达水平也降低;高半胱氨酸饮食组大鼠血浆总同型半胱氨酸浓度,以及冠状动脉内皮单核细胞趋化蛋白1的表达水平与正常饮食对照组比较差异无显著性。结论高同型半胱氨酸血症促进了大鼠冠状动脉内皮细胞表达单核细胞趋化蛋白1,在冠状动脉粥样硬化性心脏病的发生和发展中起着重要的作用。     

Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown

The role of tumor necrosis factor-alpha (TNF-alpha) as a mediator of cigarette smoke-induced disease is controversial. We exposed mice with knocked-out p55/p75 TNF-alpha receptors (TNF-alpha-RKO mice) to cigarette smoke and compared them with control mice. Two hours after smoke exposure, increases in gene expression of TNF-alpha, neutrophil chemoattractant, macrophage inflammatory protein-2, and macrophage chemoattractant, protein-1 were seen in control mice. By 6 hours, TNF-alpha, macrophage inflammatory protein-2, and macrophage chemoattractant protein-1 gene expression levels had returned to control values in control mice and stayed at control values through 24 hours. In TNF-alpha-RKO mice, no changes in gene expression of these mediators were seen at any time. At 24 hours, control mice demonstrated increases in lavage neutrophils, macrophages, desmosine (a measure of elastin breakdown), and hydroxyproline (a measure of collagen breakdown), whereas TNF-alpha-RKO mice did not. In separate experiments, pure strain 129 mice, which produce low levels of TNF-alpha, showed no inflammatory response to smoke at 24 hours or 7 days. We conclude that TNF-alpha is central to acute smoke-induced inflammation and resulting connective tissue breakdown, the precursor of emphysema. The findings support the idea that TNF-alpha promoter polymorphisms may be of importance in determining who develops smoke-induced chronic obstructive pulmonary disease.     

单核细胞趋化蛋白-1与心肌缺血再灌注损伤的关系

心肌缺血/再灌注损伤是一个重要的临床问题,而临床上对心肌缺血/再灌注损伤的防治尚缺乏有效的方法.近年发现单核细胞趋化蛋白-1在心肌缺血再灌注的早期出现并呈动态变化,抑制其出现和发展会影响心肌缺血再灌注动物的表现和预后.对单核细胞趋化蛋白-1进行干预可能成为未来新的治疗方向.     

单核细胞趋化蛋白-1与心力衰竭

炎症是心力衰竭的重要组成部分.然而其导致心力衰竭发生、发展的详细机制仍不清楚.单核细胞趋化蛋白.1是引起慢性炎症的主要趋化因子并且在心力衰竭的发病学中起着重要作用.抗单核细胞趋化蛋白-1将是治疗心力衰竭极有希望的措施.     

Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity

Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher numbers of both CD4(+) and CD8(+) T cells than lean controls, monitored by flow cytometry. When stimulated in vitro, T cells from obese AT produced more interferon (IFN)gamma than those from controls. AT from obese animals also had more cells expressing I-A(b), a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFNgamma or T-helper 1-derived supernatant produced several chemokines and their mRNAs. Obese IFNgamma-deficient animals had significantly reduced AT expression of mRNA-encoding inflammatory genes such as tumor necrosis factor-alpha and monocyte chemoattractant protein-1, decreased AT inflammatory cell accumulation, and better glucose tolerance than control animals consuming the same diet. Obese mice doubly deficient for IFNgamma receptor and apolipoprotein (Apo)E on a mixed 129SvEv/C57BL/6 (129/B6) genetic background, despite exhibiting similar AT mRNA levels of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 as 129/B6-ApoE(-/-) controls, had decreased expression of important T cell-related genes, such as IFNgamma-inducible protein-10 and I-A(b), and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFNgamma, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity.     

Chemokines in myocardial ischemia

Chemokine expression is markedly upregulated in healing myocardial infarcts and may play an important role in regulating leukocyte infiltration and activity and in modulating infarct angiogenesis as well as fibrous tissue deposition. The CC chemokine monocyte chemoattractant protein-1/CCL2 has important effects in infarct healing. Monocyte chemoattractant protein-1 -/- mice exhibit reduced macrophage infiltration and activation, suppressed cytokine synthesis, delayed phagocytotic removal of dead cardiomyocytes, diminished myofibroblast accumulation, and decreased ventricular remodeling after myocardial infarction. Monocyte chemoattractant protein-1 may also play an important role in the development of interstitial fibrosis in ischemic noninfarctive cardiomyopathy. CXC chemokines are also induced in healing infarcts. Interleukin-8/CXCL8 may mediate neutrophil recruitment and activation and may promote neovessel formation, whereas induction of the angiostatic and antifibrotic chemokine interferon-gamma-inducible protein-10/CXCL10 may serve to prevent premature wound angiogenesis and fibrous tissue deposition in the infarct, until the injured myocardium has been cleared from dead cells and debris and a fibrin-rich provisional matrix is formed. Understanding of the role of chemokines in myocardial ischemia may result in novel strategies in the treatment of patients with ischemic heart disease.     

Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease

Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.