趋化因子受体CXCR4在乳腺癌中的表达及其临床意义

目的 探讨趋化因子受体CXCR4在人乳腺癌中的表达及其与乳腺癌预后相关因素的关系.方法 收集2004年9月-2006年1月手术切除的乳腺癌标本44例,采用RT-PCR检测CXCR4 mRNA的表达,Western blotting检测CXCR4蛋白的表达,免疫组化检测CXCR4、雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体2(HER2,又称C-erbB-2)的表达,并观察相应的临床病理指标如年龄、月经状况、淋巴结转移数目、肿瘤大小、组织学分级等.结果 免疫组化显示CXCR4主要在胞质表达,很少在细胞核表达.44例乳腺癌标本中均有不同程度的CXCR4 mRNA及蛋白表达,且其表达水平随腋窝淋巴结转移增多而增高(P<0.05).与腋窝淋巴结转移阴性者比较,腋窝淋巴结转移≥4个及1～3个者CXCR4 mRNA及蛋白表达水平显著增高(P<0.05).C-erbB-2( / )组与C-erbB-2(-/+)组比较,CXCR4 mRNA及蛋白表达水平亦显著增高(P<0.05).CXCR4 mRNA及蛋白表达水平与患者年龄、月经状况、肿瘤大小、组织学分级、ER、PR无相关性(P>0.05).结论 CXCR4可能对促进乳腺癌转移有重要作用.     

老年绝经后妇女血脂和雌激素与冠心病关系

目的:探讨老年绝经后妇女雌激素、血脂在冠心病发病中的作用。方法:对老年绝经后妇女49例冠心 病组与59例正常组雌激素水平和血脂水平进行测定。结果:老年绝经后妇女冠心病组较正常组雌激素水平 明显降低(P<0．01),TC、TG、LDL-C明显升高,HDL-C降低均呈显著性差异(P<0．01)。结论:老年绝经 后妇女雌激素水平下降,血脂代谢异常,增加了冠心病的发病率。     

尖锐湿疣患者中趋化因子受体CXCR1、CXCR4及其配体的水平

目的：测定趋化因子受体CXCR1与CXCR4及其配体在尖锐湿疣（CA）患者中的水平。方法：病程大于3个月的CA患者30例,实时定量PCR法检测外周血单个核细胞（PBMC）及皮损中CXCR1与CXCR4mRNA表达水平,流式细胞仪分析外周血白细胞CXCR1与CXCR4的表达情况,ELISA检测血清IL-8与SDF-1α的水平;设30例健康人为正常对照。结果：CX-CR4 mRNA与SDF-1α在CA患者中的水平显著高于对照组（均P〈0.01）。结论：CXCR4与SDF-1α可能参与了CA的发病机制。     

绝经后服尼尔雌醇阴道细胞雌激素变化（附54例分析）

正常妇女绝经后由于卵巢功能的减退，雌激素水平低落，引起机体及生殖器系统一系列变化，出现血管运动神经障碍，植物神经功能失调，生殖器萎缩，常常影响工作与健康。为了防止及延缓衰老进程，我们对104例绝经后准备服尼尔雌醇妇女及54例服尼尔雌醇后测定阴道细胞雌激素水平来指导临床治疗。     

CXCR4反义核酸对结肠癌细胞VEGF-C mRNA表达的影响及体外侵袭的抑制作用

目的 研究趋化因子受体CXCR4反义核酸转染对结肠癌细胞HT-29血管内皮生长因子-C(VEGF-C)mRNA功能性表达和其体外侵袭能力的影响.方法 利用自行设计的引物,借助RT-PCR技术获得两端含不同限制性酶切位点的CXCR4 cDNA片段,反向插入pcDNA 3.1( )质粒中,构建CXCR4反义真核表达载体.以脂质体转染法将质粒导入HT-29细胞,用RT-PCR检测其对HT-29细胞VEGF-C mRNA表达的影响,Western blot检测HT-29细胞CXCR4蛋白表达的变化,MTT法测定HT-29细胞的生长曲线,体外侵袭实验观察转染前后HT-29细胞体外侵袭能力的变化.结果 成功构建了CXCR4反义重组质粒.与未转染(HT-29)组表达的VEGF-C mRNA相比,CXCR4反义核酸转染(HT-29tran)组的表达量下降54.2%,而空白质粒转染(HT-29KZ)组的表达量仅下降9.4%,HT-29tran组和HT-29KZ组相比差异显著(P＜0.01).穿膜细胞百分率HT-29tran组为61.3%±5.8%,而HT-29KZ组为93.7%±7.8%,两组相比差异显著(P＜0.05).结论 CXCR4反义核酸转染可明显抑制HT-29细胞VEGF-C mRNA的表达,并可显著降低HT-29细胞的体外生长和侵袭能力.     

绝经后妇女雌激素缺乏与糖代谢关系的研究

目的：探讨绝经后妇女性激素变化与糖代谢的关系。方法：测定15例绝经前健康育龄行经妇女（A组）及23例绝经后健康妇女（B组）的雌二醇（E2），促卵泡刺激素（FSH），促黄体生成素（LH），睾酮（T）及血糖（G），胰岛素（INS）并计算胰岛素敏感指数（ISI），结果。绝经后妇女E2，ISI较绝经前妇女明显降低，而G及INS水平明显升高，线性相关分析显示，绝经后妇女E2与ISI呈显正相关，而与G，INS呈显负相关。结论：绝经后妇女存在胰岛素抵抗和糖耐量减退，而雌激素水平降低是导致其产生的原因之一。     

雌激素替代治疗对雌鼠血管内皮细胞、心脏中雌激素受体含量的影响

目的：探讨雌激素替代治疗,高脂饮食对雌鼠心脏和肺血管内皮细胞中雌激素受体含量的影响。方法;用放射配体结合法定量检测雌激素受体,分别测定去势,高脂饮食及雌激素替代治疗后雌鼠心脏及血管内皮细胞中雌激素受体含量,并对去势前后血清雌激素及血脂水平进行检测。结果：去势及高脂饮食后心脏及血管内皮细胞中雌激素受体含量均下降（P＜0．01）,但以去势为明显,雌激素替代治疗9周后雌激素受体含量明显改善;去势组雌鼠血清雌二醇水平较假手术组明显下降（P＜0．01）,胆固醇水平显著升高（P＜0．01）。结论：（1）雌激素水平明显影响雌鼠心脏和血管内皮细胞中雌激素受体的表达,高脂饮食可降低雌激素受体的含量。（2）雌激素替代治疗可改善心脏和血管内皮细胞中雌激素受体含量。     

绝经后妇女的泌尿道症状及处理

绝经后的妇女泌尿道感染增多,并有不少人多次反复发作,甚感痛苦。 　　下泌尿道及生殖管道下部均由泌尿生殖窦演化而来,所以尿道、膀胱三角区的上皮也和阴道上皮一样,同样受雌激素的影响。雌激素分泌正常时,上皮增厚、细胞内糖原丰富、局部抵抗力增强,所以成年妇女泌尿系统感染相对较少。妇女绝经后,由于雌激素水平下降、尿道黏膜也萎缩变薄,局部抵抗力下降,加之尿道、阴道与肛门临近,容易受到污染而引起泌尿道感染,导致尿急、尿频、尿痛。由于绝经后妇女尿道黏膜变薄,尿道管腔随之变宽,同时盆底肌肉张力下降,容易使排尿能力…     

卡孕栓在绝经后妇女取环术中的应用

绝经后妇女由于卵巢功能衰退,体内雌激素水平下降,其内生殖器萎缩,宫颈变硬,弹性差,使绝经后取IUD难度增大。自2009年1月～2010年3月我院计划生育门诊对30例绝经后取环妇女术前应用卡孕栓,获得满意的扩张宫颈的效果,现报道如下。     

米索前列醇在绝经后妇女取环术中的临床效果分析

绝经后妇女由于卵巢功能衰退,体内雌激素水平下降,导致生殖器萎缩,宫颈变硬,易发生宫内节育器嵌顿或异位,导致宫内节育器取出困难.2006年12月-2009年12月我院对90例绝经后妇女于取环术前2 h 应用米索前列醇阴道上药,收到满意效果,现报告如下.     

CXCL1 and CXCR2 as potential markers for vital reactions in skin contusions

Detection of the vitality of wounds is one of the most important issues in forensic practice. This study investigated mRNA and protein levels of CXCL1 and CXCR2 in skin wounds in mice and humans. Western blot analysis of CXCL1 and CXCR2 protein levels showed no difference between wounded and intact skin. However, mRNA levels demonstrated higher expression of CXCL1 and CXCR2 in contused mouse and human skin, compared with intact skin. At postmortem there were no remarkable changes in CXCL1 and CXCR2 mRNA levels in contused mouse skin. Increased mRNA expression was observed in contused mouse skin up to 96 h and 72 h after death for CXCL1 and CXCR2 respectively. In human samples of wounded skin, increased CXCL1 mRNA levels were detected up to 48 h after autopsy in all 5 cases, while increased CXCR2 mRNA levels were observed 48 h after autopsy in 4 of 5 cases. These findings suggest that the levels of CXCL1 and CXCR2 mRNA present in contused skin can be used as potential markers for a vital reaction in forensic practice.     

阿托伐他汀对2型糖尿病患者外周血单核细胞TLR4表达的影响

目的探讨阿托伐他汀对2型糖尿病的抗炎作用机制是否与抑制toll样受体4(TLR4)有关。方法将40例2型糖尿病患者随机分为常规治疗组和阿托伐他汀治疗组。阿托伐他汀治疗组患者在常规治疗基础上给予阿托伐他汀20 mg,1次/d,晚间口服。治疗前及治疗1月后采血,应用流式细胞仪检测外周血单核细胞TLR4蛋白表达;应用酶联免疫(ELISA)法检测血浆肿瘤坏死因子-α(TNF-α)浓度。结果单核细胞TLR4蛋白与血糖,糖化血红蛋白及血浆TNF-α呈正相关。治疗1月后,阿托伐他汀治疗组和常规治疗组血糖、外周血单核细胞TLR4蛋白及血浆TNF-α浓度均较治疗前降低(P<0.05);阿托伐他汀治疗组单核细胞TLR4蛋白和血浆TNF-α均低于常规治疗组(P<0.05)。结论阿托伐他汀能下调2型糖尿病患者的单核细胞TLR4表达,降低血浆炎症因子水平。其抗炎作用可能与抑制单核细胞TLR4通路有关。     

Quantitation of CXCR4 expression in myocardial infarction using 99mTc-labeled SDF-1alpha.

The chemokine stromal-derived factor-1alpha (SDF-1alpha, CXCL12) and its receptor CXCR4 are implicated as key mediators of hematopoietic stem cell retention, cancer metastasis, and HIV infection. Their role in myocardial infarction (MI) is not as well defined. The noninvasive in vivo quantitation of CXCR4 expression is central to understanding its importance in these diverse processes as well in the cardiac response to injury. METHODS: Recombinant SDF-1alpha was radiolabeled under aprotic conditions and purified by gel-filtration chromatography (GFC) using high-specific-activity 99mTc-S-acetylmercaptoacetyltriserine-N-hydroxysuccinimide ([99mTc-MAS3]-NHS) prepared by solid-phase preloading. Radiotracer stability and transmetallation under harsh conditions were quantified by GFC. Affinity, specificity, and maximum number of binding sites (Bmax) were quantified, with adenoviral-expressed CXCR4 on nonexpressing cells and endogenous receptor on rat neonatal cardiomyocytes, using a high-throughput live-cell-binding assay. Blood half-life, biodistribution, and clearance of intravenously injected [99mTc-MAS3]-SDF-1alpha were quantified in Sprague-Dawley rats before and after experimentally induced MI. RESULTS: [99mTc-MAS3]-SDF-1alpha could be prepared in 2 h total with a specific activity of 8.0 x 10(7) MBq/mmol (2,166 Ci/mmol) and a radiochemical purity greater than 98%. Degradation of the radiotracer after boiling for 5 min, with and without 1 mM dithiothreitol, and transmetallation in 100% serum at 37 degrees C for 4 h were negligible. [99mTc-MAS3]-SDF-1alpha exhibits high specificity for CXCR4 on the surface of living rat neonatal cardiomyocytes, with an affinity of 2.7 +/- 0.9 nM and a Bmax of 4.8 x 10(4) binding sites per cell. After intravenous injection, 99mTc-labeled SDF-1alpha displays a blood half-life of 25.8 +/- 4.6 min, rapid renal clearance with only 26.2 +/- 6.1 percentage injected dose remaining in the carcass at 2 h, consistently low uptake in most organs (<0.1 percentage injected dose per gram), and no evidence of blood-brain barrier penetration. After MI was induced, CXCR4 expression levels in the myocardium increased more than 5-fold, as quantified using [99mTc-MAS3]-SDF-1alpha and confirmed using confocal immunofluorescence. CONCLUSION: We describe a 99mTc-labeled SDF-1alpha radiotracer that can be used as a sensitive and specific probe for CXCR4 expression in vivo and demonstrate that this radiotracer is able to quantify changes in CXCR4 expression under different physiologic and pathologic states. Taken together, CXCR4 levels should now be quantifiable in vivo in a variety of animal model systems of human diseases.     

2型糖尿病患者外周血单核细胞三磷酸腺苷结合盒转运体A1的变化及其意义

目的初步分析2型糖尿病患者血脂及外周血单核细胞三磷酸腺苷结合盒转运体A1(ABCA1)的变化,以及2型糖尿病患者ABCA1的变化与血脂、糖代谢的相关性。方法分别取2型糖尿病组及对照组(各40例)外周血中的单核细胞,利用抗原、特异性一抗及PE荧光标记的二抗间的相互反应,在流式细胞仪上检测氧化型低密度脂蛋白(ox-LDL)刺激前后ABCA1的表达变化,同时在空腹情况下检测血脂及空腹血糖(FPG)、糖化血红蛋白(HbA1C)。分析2型糖尿病患者ABCA1表达变化与年龄、血脂水平和糖代谢的相关性。结果与对照组相比,2型糖尿病组甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和极低密度脂蛋白胆固醇(VLDL-C)[即非高密度脂蛋白胆固醇(NHDL-C)]水平显著升高(P<0.01),血清高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(apoA1)的水平及外周血单核细胞ABCA1的表达显著降低(P<0.01)。ox-LDL刺激24h后,2型糖尿病组ABCA1的变化量(刺激后表达量/初始表达量)明显高于对照组ABCA1的变化量(P<0.01),但最终表达量仍显著低于对照组(P<0.01);ox-LDL刺激后2型糖尿病组AB-CA1的改变量与HDL-C呈正相关。结论2型糖尿病患者体内存在受损的胆固醇逆转运及血脂谱,具有诱发动脉粥样硬化(AS)和冠心病的基础。     

CXC型趋化因子受体4及其分子显像剂在肿瘤方面的研究进展

CXC型趋化因子受体4（CXCR4）及CXC型趋化因子配体12（CXCL12）在肿瘤生长、新生血管形成和远处转移等方面发挥了至关重要的作用。两者结合后可以激活下游信号通路,从而发挥促进肿瘤生长和血管生成的作用。肿瘤组织高表达CXCR4,而肿瘤较常发生转移的部位高表达CXCL12,两者之间可通过特异性的结合而促使肿瘤发生转移。因此,CXCR4的表达水平在肿瘤转移的诊断方面具有预示性的作用,而无创性的影像学诊断方法,如SPECT/CT、PET显像等,有望在CXCR4的显像方面发挥重要作用,从而实现肿瘤的早期诊断和早期治疗。     

肥胖人群外周血单核细胞TLR4表达变化及他汀干预作用的研究

目的探讨肥胖人群外周血toll样受体4(TLR4)表达的变化及应用他汀类药物的作用机制是否与抑制toll样受体4(TLR4)有关。方法 57例肥胖者随机分为常规对照组和阿托伐他汀干预组,阿托伐他汀干预组给予阿托伐他汀20 mg/晚,用药前及用药后1个月采血,应用流式细胞仪检测外周血单核细胞TLR4蛋白表达;应用ELISA法检测血浆TNF-α浓度。结果单核细胞TLR4蛋白与体质量及血浆TNF-α正相关。用阿托伐他汀干预1个月后,阿托伐他汀干预组外周血单核细胞TLR4蛋白及血浆TNF-α浓度均较干预前降低(P<0.05);阿托伐他汀治疗组单核细胞TLR4蛋白和血浆TNF-α低于常规对照组(P<0.05)。结论阿托伐他汀能下调肥胖人群单核细胞TLR4表达,降低血浆炎症因子水平。其抗炎作用可能与抑制单核细胞TLR4通路有关。     

Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors

The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For 111In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of d-Lys(8) which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more 111In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that 111In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.     

The effect of hormone replacement therapy and exercise on cardiovascular disease risk factors in postmenopausal women

Following menopause, women show an increased risk of heart disease to a level equal that of men. This elevated risk is thought to be due, at least partly, to changes in blood lipid and fibrinogen levels. The purpose of this article is to review the published research on the relationship between both exercise and hormone replacement with regards to common cardiovascular disease (CVD) risk factors and the relative importance of each. Menopause is associated with increased total serum cholesterol, triglycerides and fibrinogen, and a decrease in high density lipoprotein (HDL) cholesterol levels. The major reason for these changes following menopause is believed to be a result of fluctuations in hormonal status, primarily a deficiency in estrogen. Intervention may be justified since estrogen replacement therapy has been shown to decrease the risk of developing CVD and to have a significant impact on many of the CVD risk factors. The results vary from study to study, but generally estrogen replacement has been found to decrease total cholesterol and fibrinogen, while increasing HDL cholesterol and triglycerides. All of these changes, other than the increase in triglycerides, are seen as positive. The addition of progestogen to estrogen may negate some of the beneficial changes of estrogen, most notably the increase in HDL cholesterol levels. However, progestogen has also been reported to offset the increase in triglycerides seen with unopposed estrogen replacement. Thus, there are contradictory effects (both positive and negative) of hormone replacement on CVD risk factors in women. Regular aerobic exercise and resulting improvements in cardiorespiratory fitness have consistently been shown as preventive of CVD. This decreased CVD risk is in part because of the impact of exercise on blood lipids and fibrinogen. Increased aerobic exercise is thought to improve the risk profile, mainly through an increase in HDL cholesterol levels and decreases in triglycerides and fibrinogen. Unfortunately, the majority of research supporting the effects of exercise on CVD risk factors has been done on men. Even when research has included women, very few studies have focused on postmenopausal women. However, the research done on postmenopausal women points to a significantly improved CVD risk factor profile with regular cardiorespiratory exercise.