乙酰肝素酶在子宫内膜异位症中的研究进展

乙酰肝素酶(HPA)可降解细胞外基质(ECM)和基底膜(BM)中的硫酸乙酰肝素蛋白聚糖(HSPGs)成分,并促进血管生成,在子寓内膜异位症(Endometriosis,EMS)的发生和发展中发挥重要的作用。EMS的浸润、转移等类似恶性临床行为主要是因为ECM和BM的完整性被破坏所致。目前随着对HPA分子生物学特性、尤其对其抑制剂等方面研究的不断深入,为EMS防治提供了新的方向。     

syndecan-4与肾小球肾炎系膜增殖关系的探讨

syndecan-4是一种跨膜硫酸乙酰肝素蛋白聚糖（HSPG），广泛表达于哺乳动物细胞膜上，属于Ⅰ型跨膜糖蛋白。已经有研究认为它对多种肾脏疾病的发生有重要意义，其胞外区的硫酸乙酰肝素（heparan sulfate，HS）链能与许多潜在的配体包括生长因子及细胞外基质大分子等相互作用，参与多种生物学功能如生长因子信号转导、细胞增殖，介导细胞及细胞外基质的粘附及组织损伤反应等。     

乙酰肝素酶在妇产科的研究进展

乙酰肝素酶(Hpa)是裂解细胞外基质(ECM)和细胞基底膜(BM)中乙酰硫酸肝素盐蛋白聚糖(HSPGs)中乙酰硫酸肝素盐(HS)的内源葡萄糖醛酸酶的统称。大量的研究发现Hpa广泛存在与细胞滋养层细胞、内皮细胞、血小板、乳突细胞、角质层细胞、嗜中性粒细胞、巨噬细胞、T、B淋巴细胞、淋巴瘤细胞、黑色素细胞和癌细胞等细胞中。它在妊娠、组织形成、炎症、血管生成和肿瘤转移等生理和病理过程中发挥着重要作用。Hpa与妇产科许多疾病之间有密切的联系。本文根据所查阅的有关文献,就乙酰肝素酶在妇产科领域中的研究进展做一综述。1Hpa简介HSPGs作…     

串珠素调节肿瘤血管生成的研究进展

串珠素（perlecan，PN）是细胞外基质（extracellularmatrix，ECM）中硫酸肝素类蛋白聚糖之一。由核心蛋白和4条硫酸肝素（heperin sulfate，HS）侧链组成，鼠类串珠素的分子量约为700kD，其核心蛋白含5个功能区，分子量约390kD，串珠素核心蛋白的N端附着有3条长的HS侧链，核心蛋白功能区V上还有一个HS侧链的附着位点。串珠素在软骨、骨骼肌和心血管组织发育中的作用已经被证实。串珠素通过与血管壁生长因子相互作用而调节肿瘤血管生成，其在肿瘤新生血管形成中的作用开始受到关注。     

乙酰肝素酶与妇产科疾病关系的研究进展

对广泛存在于妇产科领域里的生理及病理变化 ,如胚胎组织发育 ,孕期及分娩时母体子宫血管变化、肌纤维和胶原纤维增生 ,生殖系统感染性疾病 ,甚至宫颈癌、卵巢癌的浸润和转移等 ,目前认为与体内一种被称为乙酰肝素酶的物质有关〔1〕。乙酰肝素 (Heparan Sulfate Proteoglycans,HSPGs) ,又称硫酸乙酰肝素多聚糖 ,是一种蛋白聚糖类碳水化合物 ,为广泛存在于有脊椎动物和无脊椎动物组织细胞外基质 (ECM)和细胞表面的牛物大分子 ,是基底膜的主要构成成分 〔2 ,3〕。它能与细胞表面及 ECM中的活性分子结合 ,粘附于细胞表面 ,是 ECM聚集和…     

基质金属蛋白酶及其抑制物与子宫内膜异位症及子宫腺肌病关系的研究新进展

1基质金属蛋白酶及其抑制物 1．1基质金属蛋白酶 基质金属蛋白酶（matrix metalloproteinases，MMPs）是自然界中高度保守的一类酶，可降解细胞外基质（extracellular matrix，ECM）。MMPs广泛分布于植物、脊椎动物、无脊椎动物中。目前至少发现20种MMPs。它们几乎能降解ECM的所有成分。生理状态下，MMPs能参与细胞迁移和ECM的重建；病理状态下，参与ECM分解的疾病。     

乙酰肝素酶在子宫颈癌组织中的表达与肿瘤转移及血管形成的关系

目的:乙酰肝素酶是一类裂解硫酸乙酰肝素的糖苷内切酶,通过降解肿瘤细胞细胞外基质和基底膜以及诱导新生血管的形成而促进肿瘤扩散和转移。本研究探讨子宫颈癌组织中乙酰肝素酶的表达与子宫颈癌转移及血管生成的关系。方法:应用免疫组织化学SABC法检测50例子宫颈鳞癌、12例子宫颈腺癌、10例子宫颈正常组织中乙酰肝素酶的表达情况及微血管密度(MVD)。结果:子宫颈癌中乙酰肝素酶的表达率(62.9%)明显高于其在子宫颈正常组织中的表达率。在子宫颈癌组织中的阳性表达率与子宫颈癌的临床分期、肿瘤直径大小以及有无淋巴结转移密切相关,P均<0.05。子宫颈正常组织、子宫颈癌组织中MVD的平均值分别为(11.33±2.38)、(42.97±9.99)(P=0.00)。子宫颈癌组织中乙酰肝素酶的阳性表达组MVD显著高于其阴性表达组MVD,P<0.05。结论:乙酰肝素酶在子宫颈癌的浸润、转移及血管生成过程中起重要作用。     

明胶酶及其抑制剂与胶质瘤侵袭性生长之间的关系

胶质瘤侵袭性生长的生物学特性使各种治疗措施难以达到治愈目的。胶质瘤细胞的侵袭行为涉及细胞迁移和附加降解的功能，即指肿瘤细胞通过释放蛋白溶解酶使细胞外基质（exlxacellular matrix, ECM）屏障降解的能力。蛋白酶对ECM的降解是肿瘤细胞侵袭转移的关键，是肿瘤侵袭性的标志。基质金属蛋白酶marx metalloproteinase，MMP）是一类重要的Zn^2＋依赖的内源性金属蛋白酶，[第一段]     

肝素及其降解片段对急性呼吸窘迫综合征细胞外组蛋白拮抗作用的比较

目的比较肝素（heparan sulfate,HS）及其片段在大鼠急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）发病中对细胞外组蛋白的拮抗作用,研究肝素降解在炎症发展中的作用。方法实验设对照组、CTH损伤组、肝素片段dp4、dp10组和肝素干预组,每组6只大鼠。CTH损伤组经股静脉注射小牛胸腺组蛋白（calf thymus histone,CTH）复制大鼠ARDS模型,对照组给予等量生理盐水。干预组经腹腔注射给予肝素或肝素片段（10 mg/kg,每6 h 1次,24 h）进行干预。检测肺湿/干重比值、支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）中蛋白含量、白细胞数量,光学显微镜下观察中性粒细胞数量、肺组织病理的改变。结果CTH损伤组大鼠的肺湿/干重比值、BALF中蛋白浓度、白细胞和中性粒细胞数量均明显高于对照组,差异有统计学意义（P〈0.01）。肝素干预组肺湿/干重比值、BALF中蛋白浓度、白细胞和中性粒细胞数量均明显低于CTH损伤组,差异有统计学意义（P〈0.05）。肝素片段dp10干预组BALF中蛋白浓度和BALF中白细胞数量明显低于CTH损伤组,差异有统计学意义（P〈0.05）。dp10干预组的肺湿/干重比值、BALF中中性粒细胞数量均低于CTH损伤组,差异均无统计学意义（P〉0.05）。肝素片段dp4干预组肺湿/干重比值、BALF中蛋白浓度、白细胞数量和中性粒细胞数量低于CTH损伤组,差异均无统计学意义（P〉0.05）。光学显微镜下可见CTH损伤组大鼠的肺组织出血、水肿、肺泡间质增厚,肺泡中弥漫分布炎症细胞。肝素片段和肝素干预组的肺组织病变程度要比CTH损伤组明显改善,而且肝素干预组的肺组织损伤程度轻于肝素片段干预组。结论肝素和肝素片段对CTH导致的肺损伤具均有防护效果,肝素全长优于肝素片段。     

Smad蛋白——肝纤维化时TGF-β1信号转导的关键物质

肝纤维化的发生是由于细胞外基质的合成与降解的失衡造成的,而细胞外基质(ECM)的主要来源就是肝星形细胞(HSC),HSC的活化、增殖、数量增加,从而使细胞外基质的合成增加、降解减少、平衡破坏,是肝纤维化发生发展的关键因素。TGF-β1正是促进HSC活化、ECM合成的主要起始因子,而Smads蛋白是TGF-β超家族最重要的胞内效应分子。在肝纤维化的过程中,TGF-β1/Smad信号转导对HSC的作用非常重要,它在ECM表达调节中的作用是研究肝纤维化的关键。本文就TGF-β1/Smad信号转导与调控、及其在肝纤维化发生发展过程中的作用进行阐述。     

The effect of extracellular matrix molecules on mouse preimplantation embryo development in vitro

The extracellular matrix (ECM) molecules, laminin (LN), chondroitin sulfate (CS), fibronectin (FN), hyaluronic acid (HA), mucin (MUC) and heparan sulfate proteoglycan (HS), were investigated as supplements to culture medium to improve the in vitro development of mouse 1-cell zygotes to blastocysts. Development was also compared with that in medium supplemented with bovine serum albumin (BSA) to determine the potential for ECM molecules as suitable alternatives to serum albumin in culture medium. Supplementation of sequential culture media with LN at all concentrations examined failed to result in more than 70% of zygotes developing to blastocysts; therefore, LN was considered unsuitable as a replacement for BSA and was not examined further. The optimal concentration of the remaining ECM molecules was used to supplement sequential culture media and the effect on blastocyst quality was assessed by determining the differential cell numbers of blastocysts grown in BSA-supplemented medium. Development to blastocyst was similar, regardless of the macromolecule used. The number of inner cell mass cells was significantly higher in HS-supplemented medium compared with controls. Trophectoderm cell numbers were similar to control values for all ECM molecules examined except CS for which there were fewer trophectoderm cells. It is concluded that ECM molecules, FN, HA, MUC and HS may be used as substitutes for serum protein supplementation of culture media EG0/G2 for mouse preimplantation embryo development. Heparan sulfate proteoglycan increases inner cell mass numbers and this may be due to interactions with the growth factors fibroblast growth factor 4 (FGF-4) and granulocyte-macrophage colony-stimulating factor.     

血清标记物GPC3与肝细胞癌的研究进展

磷脂酰肌醇蛋白多糖-3（glypican-3,GPC3）是一种硫酸乙酰肝素糖蛋白,研究证明,GPC3表达与肝细胞癌（HCC）关系密切,尤其是小肝癌、AFP（甲胎蛋白）阴性肝癌、早期肝癌新的血清标志物。联合检测多种肿瘤标志物能大大提高诊断效能,为提高HCC诊断敏感性和特异性,现对血清GPC3与肝细胞癌关系进行综述。     

靶向结缔组织生长因子siRNA对肝纤维化影响研究进展

肝纤维化是肝脏对各种原因所致肝损伤的创伤愈合反映,是组织发生修复反映时细胞外基质(ECM)合成、降解与沉积不平衡而引起的病理过程,肝纤维化的形成涉及多种细胞、细胞因子以及ECM的变化.其中肝星状细胞(HSCs)激活并转化为肌成纤维细胞是肝纤维化发生、发展的核心环节、各种致纤维化因素均把HSCS作为最终靶细胞,促使其转化为肌成纤维细胞而导致肝纤维化的发生.影响肝纤维化形成的因素很多,至今尚未完全阐明.结缔组织生长因子(connective tissue growth factor,CTGF)是一种非结构性基质蛋白,能直接介导肝星状细胞(HSCs)的活化、合成及分泌细胞外基质(ECM),该因子的研究为探索肝纤维化的发病机制及新的治疗方案注入了新思想,现就CTGF在肝纤维化中研究讲展作一综述.     

Syndecan-1 mediates internalization of apoE-VLDL through a low density lipoprotein receptor-related protein (LRP)-independent, non-clathrin-mediated pathway

Background  

Triacylglyerol-rich very low density lipoprotein (VLDL) particles are the primary carriers of fatty acids in the circulation and as such serve as a rich energy source for peripheral tissues. Receptor-mediated uptake of these particles is dependent upon prior association with apolipoprotein E (apoE-VLDL) and is brought about by cell surface heparan sulfate proteoglycans (HSPG) in some cell types and by the low density lipoprotein receptor-related protein (LRP) in others. Although LRP's role in apoE-VLDL uptake has been well studied, the identity of the HSPG family member that mediates apoE-VLDL uptake has not been established. We investigated if syndecan-1 (Syn-1), a transmembrane cell surface HSPG, is able to mediate the internalization of apoE-VLDL and examined the relationship between Syn-1 and LRP toward apoE-VLDL uptake. For this study, we used a human fibroblast cell line (GM00701) that expresses large amounts of LRP, but possesses no LDL receptor activity to eliminate its contributions toward apoE-VLDL uptake.     

硫酸铟对V79细胞内活性氧和线粒体膜电位的影响

[目的]观察硫酸铟对中国仓鼠肺纤维细胞（V79细胞）内活性氧（ROS）和线粒体膜电位的影响。[方法]不同浓度硫酸铟（0.5、1.0、2.0、4.0、8.0mmol/L）染毒体外培养的V79细胞,MTT法检测细胞存活率;以2’,7’-荧光素乙二酯和碘化四氯代四乙基苯咪唑羰花青为探针,采用流式细胞术,检测经不同浓度硫酸铟染毒12h后V79细胞内ROS和线粒体膜电位的水平。[结果]硫酸铟能明显降低V79细胞的存活率;不同浓度硫酸铟作用于V79细胞12h后,细胞内的平均荧光强度从21.60增加到31.10,线粒体膜电位从0.1913降低到0.1090,与对照组相比,差异有统计学意义（P〈0.05）。[结论]硫酸铟能增加V79细胞内ROS的释放、降低线粒体膜电位,影响细胞的正常代谢功能,对细胞造成损伤。     

Cell surface heparan sulfate proteoglycans contribute to intracellular lipid accumulation in adipocytes

Background  

Transport of fatty acids within the cytosol of adipocytes and their subsequent assimilation into lipid droplets has been thoroughly investigated; however, the mechanism by which fatty acids are transported across the plasma membrane from the extracellular environment remains unclear. Since triacylglycerol-rich lipoproteins represent an abundant source of fatty acids for adipocyte utilization, we have investigated the expression levels of cell surface lipoprotein receptors and their functional contributions toward intracellular lipid accumulation; these include very low density lipoprotein receptor (VLDL-R), low density lipoprotein receptor-related protein (LRP), and heparan sulfate proteoglycans (HSPG).     

Effect of hyperglycemic condition on proteoglycan secretion in cultured human endothelial cells

Background Proteoglycans (PGs) are important constituents of the plasma membrane and of the basement membrane supporting the endothelial cell layer. Changes in the amounts or the structures of PGs in the endothelium may affect important functions such as turnover of lipoproteins, filtration properties, and regulation of chemokines during inflammation, which are all relevant in diabetes. Aim of the study The purpose of this study was to investigate if hyperglycemic conditions would affect the biosynthesis and secretion of PGs in cultured primary human endothelial cells. Methods Primary human umbilical cord vein endothelial cells were established and cultured in vitro. The cells were cultured either in medium with low glucose (LG) (1 g/l) or high glucose (HG) (4.5 g/l). From day 3–4 cells were labeled with ³⁵S-sulfate for 24 h. ³⁵S-Labeled macromolecules (medium) were purified by gel chromatography, and isolated macromolecules were analyzed by gel chromatography after different types of treatment, electrophoresis, and immunoprecipitation. Results Lower levels of secreted PGs were found in human endothelial cells exposed to HG. The major part of the PGs released was of the heparan sulfate (HS) type, and immunoprecipitation experiments showed that one such PG was syndecan-1. However, there was no difference in the ratio between HS and chondroitin sulfate (CS) under the different experimental conditions. Further, the PGs expressed neither differ with regard to molecular size of the glycosaminoglycan (GAG) chains, nor were their polyanionic properties affected by the different experimental conditions. Conclusion: The results obtained suggest that treatment of primary human endothelial cells with hyperglycemia leads to a decrease in PG secretion in primary cultures of human endothelial cells.     

经阴道超声及宫腔镜诊断子宫内膜息肉的价值对比分析

目的探讨利用阴道超声结合宫腔镜检查提高子宫内膜息肉的检出率。方法通过对67例临床怀疑子宫内膜息肉的患者行经阴道彩超及宫腔镜检查,并病理最后确诊子宫内膜息肉,探讨二者在该疾病中的诊断价值及对比分析。结果经阴道超声(TVS)检查对子宫内膜息肉诊断的敏感性和特异性分别为84.5%和81.7%;宫腔镜(HS)对子宫内膜息肉诊断的敏感性和特异性分别为91.9%和95%。结论经阴道超声能够清晰显示子宫内膜息肉的部位、个数、大小,但要明确病变性质,其敏感性和特异性不如HS,二者的有机结合可以有效提高子宫内膜息肉的诊治效率。     

皖北地区1～16岁儿童麻疹、风疹、流脑、乙脑抗体水平调查

目的 了解皖北地区儿童麻疹病毒IgG、风疹病毒IgG、A群流行性脑脊髓膜炎IgG和流行性乙型脑炎病毒IgG 4种免疫抗体水平.方法 采用整群抽样的方法,共采集1 ～16岁儿童手指血清样品5 542份,采用酶联免疫吸附试验法(enzyme-linked immunosorbent assay,ELISA)进行上述4种病毒IgG抗体水平监测.结果 在调查的5 542份有效样本中,麻疹病毒、风疹病毒、A群流行性脑脊髓膜炎和流行性乙型脑炎病毒IgG抗体阳性率分别为95.9％、92.5％、89.4％和94.2％.结论 皖北地区1～16岁儿童麻疹病毒IgG抗体、风疹病毒IgG抗体、A群流行性脑脊髓膜炎IgG抗体和流行性乙型脑炎病毒IgG抗体具有较高水平,形成了较牢固的免疫屏障,对控制上述4种传染病的暴发和流行起到了较好的作用.     

老年冠心病患者超敏C反应蛋白与血脂联合检测结果分析

目的探讨老年冠心病患者超敏c反应蛋白和血脂检测分析的临床意义。方法测定180例老年冠心病患者和150例老年正常对照组血清超敏c反应蛋白（HS—CRP）、总胆固醇（Tc）,甘油三脂（TG）、高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）、载脂蛋白A1（ApoA1）、载脂蛋白B（ApoB）、脂蛋白（a）[Lp（a）]水平并进行统计学分析。结果180例老年冠心病患者和t50例正常对照组HS—CRP、TC、TG、LDL—C、ApoB、Lp（a）均显著高于正常组（P〈0．01）,HDL—C、ApoA1低于正常组（P〈0．01）。结论Hs—CRP是心血管疾病的独立危险因素,冠心病患者HS—CRP与血脂代谢异常有相关性;其与血脂联合检测对老年冠心病的诊断和治疗有重要意义。