细胞外基质与PTCA术后再狭窄

ＰＴＣＡ术后再狭窄，细胞外基质发挥重要作用，西方讨论了细胞外基质与ＰＴＣＡ术后再狭窄的关系；基质成份合成、积累与降解过程；基质成份基因表达；基质与平滑纲细胞的增殖、迁移关系；基质在血管再塑型中的作用。     

细胞外基质在血管平滑肌细胞迁移中的作用

血管损伤后新生内膜形成的过程,也是基质重建的过程,一方面血管平滑肌细胞增生、迁移,分泌大量的细胞外基质,另一方面又产生基质金属蛋白酶使基质不和解,最终导致再狭窄的发生。     

益气活血软坚解毒方含药血清诱导人肝癌细胞系Bel-7402细胞凋亡过程中部分凋亡调控基因变化

目的:研究益气活血软坚解毒方(YHRJ)含药血清对人肝癌细胞系Bel-7402细胞凋亡调控基因Fas,FasL,Bcl-2,Bax,P53,NF-kB表达影响.方法:将细胞分为对照组(NS)组、NS DDP(顺氯氨铂)组、YHRJ等剂量组(YHRJD)、YHRJD DDP组、YHRJ高剂量组(YHRJG)、YHRJG DDP组,应用流式细胞术、免疫组化、原位杂交、RT-PCR等方法对用药24,48h的Bel-7402细胞凋亡的主要调控基因Fas,FasL,Bcl-2,Bax,P53,NF-kBmRNA与蛋白表达进行检测.结果:流式细胞术检测显示:与NS组相比,NS DDP、YHRJD、YHRJD DDP及YHRJG DDP组Fas蛋白表达均明显提高(30.12%±22.94%,10.50%±8.41%,30.35%±22.98%,32.61%±26.87%vs8.77%±6.93%,P<0.01),YHRJG组效果不明显(P>0.05);NS DDP、YHRJD DDP组FasL蛋白表达也升高(16.40%±7.168%,8.41%±6.74%vs4.12%±2.60%,P<0.01),而YHRJG组FasL蛋白表达降低(3.05%±2.53%vs4.12%±2.60%,P<0.01).免疫组化结果显示:除YHRJG DDP组外,其余各组突变型P53蛋白表达明显降低(30.2%,14.6%,19.8%,17.3%vs60.0%,P<0.05);各加药组Bax蛋白表达明显增高(40.7%,40.4%,72.1%,68.9%,42.2%vs30.0%,P<0.05);NS DDP组与YHRJG组Bcl-2蛋白表达明显降低(26.3%,24.4%vs30.5%,P<0.05),而YHRJD、YHRJG DDP、YHRJG DDP组Bcl-2表达明显升高(41.8%,39.3%,45.6%vs30.5%,P<0.05);各加药组NF-kB蛋白表达明显降低(15.9%,13.3%,14.1%,7.8%,14.6%vs24.2%,P<0.05).原位杂交结果显示:各加药组NF-kBmRNA表达明显降低(30.5%,13.3%,21.4%,17.4%,53.2%vs58%,P<0.05).RT-PCR结果显示:YHRJ等效剂组凋亡调控基因Bcl-2mRNA表达明显降低(0.717±0.198vs1.327±0.097,P<0.001);DDP、YHRJD、YHRJG组凋亡调控基因BaxmRNA表达明显增高(46.22±6.22,56.19±7.36,62.32±11.06vs35.22±4.38,P<0.05).结论:YHRJ含药血清诱导人肝癌细胞系Bel-7402细胞凋亡可能的基因调控机制在于通过抑制凋亡信号转导基因FasL基因蛋白表达,促进凋亡调控基因Bax基因蛋白表达,抑制NF-kB基因mRNA及蛋白表达来实现的.     

磺酸抑制实验性肝纤维化大鼠细胞外基质沉积

目的 研究牛磺酸抗肝纤维化作用。方法 用四氯化碳（ＣＣｌ４）制备肝纤维化模型;免疫化检测肝Ｉ,Ⅲ,Ⅳ型胶原和透明质酸,层粘连素沉积;Ｎｏｒｔｈｅｒｎ ｂｌｏｔ杂交检测肝Ｉ,Ⅲ,Ⅳ型肝原,透明质酸和层粘连素染色显增多,Ｉ,Ⅲ,型前胶原,ＴＩＭＰ－１ ｍＲＮＡ显著增加,牛磺酸处理的大鼠,上述各种指标的阳性色明显减少,并可明显抑制Ⅰ、Ⅲ型前胶原基因表达,而对ＴＩＭＰ－１ ｍＰＮＡ却无明显影响。结论 牛磺     

大鼠肺细胞外基质老化的实验研究

目的观察细胞外基质（ＥＣＭ）在肺老化中的作用。方法利用免疫组化技术和生化测定方法，观察肺老化时ＥＣＭ成分相对含量，在不同年龄组间进行对比分析。结果纤维粘连蛋白（Ｆｎ），老年大鼠（０．１４±０．０４）较中年大鼠（０．０８±０．０２）、幼年大鼠（０．０８±０．０１）增多；层粘连蛋白（Ｌｎ），老年大鼠（０．０５±０．０１）较中年大鼠（０．１０±０．０２）、幼年大鼠（０．１６±０．０３）减少；Ⅳ型胶原，老年大鼠（０．０８±０．０２）较中年大鼠（０．１１±０．０２）、幼年大鼠（０．１８±０．０５）减少。各年龄组间氨基多糖（ＧＡＧ）总量未见明显改变，但其成分构成比发生了一些改变，和中、幼年鼠相比，老年鼠肺透明质酸减少，硫酸肝素相应增高。结论推测这些变化与肺老化存在着一定的联系     

益气活血化瘀方治疗帕金森病的疗效观察

目的 观察自拟益气活血化瘀方治疗气虚血瘀型帕金森病的临床疗效.方法 将53例患者随机分为观察组(27例)与对照组(26例).对照组口服多巴丝肼片;观察组在对照组基础上加自拟益气活血化瘀方治疗.观察两组治疗前后血液流变学、血脂指标和颅多普勒超声(TCD)的变化.结果观察组治疗后血脂、血液流变学、TCD指标明显改善(P<0.05或P<0.01),且观察组较对照组改善明显(P<0.05或P<0.01).结论 自拟益气活血化瘀方可明显改善气虚血瘀型帕金森病的临床症状.     

肝脏细胞外基质与细胞的相互作用

对肝纤维化发病机制的深入研究发现，肝内细胞产生细胞外基质，尤其是Ｉｔｏ细胞，是细胞外基质的主要来源，肝内细胞还分泌各种细胞因子调节细胞外基质的合成。细胞外基质影响细胞的功能。它不仅是支架，从结构上把各咱细胞连成一个整体，还具调节功能，从机能上把各种细胞有机地结合在一起。     

益气活血解毒方对晚期卵巢癌患者免疫功能及生活质量的影响

目的探讨益气活血解毒方对晚期卵巢癌患者免疫功能及生活质量的影响。方法 50例晚期卵巢癌患者按随机数字表法分为对照组和试验组各25例。两组均接受紫杉醇联合顺铂(TP)化疗方案治疗,试验组在此基础上给予益气活血解毒方治疗,连续治疗28 d。检测并比较两组治疗前后血清CD4~+CD25~+、CD8~+CD28-及CD8~+CD28~+的水平。评价并比较两组治疗后卡氏评分(KPS)和生活质量改善情况。结果治疗后两组血清CD4~+CD25~+、CD8~+CD28-水平明显降低,血清CD8~+CD28~+水平明显升高(P<0.05),且试验组改善明显优于对照组(P<0.05)。治疗后两组KPS评分均明显高于治疗前,且试验组明显高于对照组(P<0.05)。治疗后试验组生活质量改善率明显高于对照组(χ2=4.500,P=0.034)。结论益气活血解毒方能够明显改善行TP化疗方案后的晚期卵巢癌患者的免疫功能和生活质量。     

重视肝纤维化细胞外基质降解中TIMPs的研究

在正常肝脏纤维组织中存在着细胞外基质(ＥＣＭ)的合成与降解的动态平衡 ,肝纤维化及肝硬化时纤维结缔组织的形成 ,是各种不同致病因子导致ＥＣＭ合成与降解的失衡所致。纤维组织的形成不是一个静止过程 ,而是一个动态过程 ,因此 ,研究肝纤维化及早期肝硬化的可逆性 ,在注意胶原合成过程的同时 ,应加强胶原降解过程的研究。1　胶原降解主要由基质金属蛋白酶 (ＭＭＰｓ)介导既往对肝纤维化ＥＣＭ合成与沉积的研究比较深入。ＥＣＭ主要由胶原以及蛋白多糖、糖蛋白等组成 ,肝星状细胞 (ＨＳＣ)是其主要来源。处于“静止”期的ＨＳＣ主要合成Ⅳ…     

骨桥蛋白和基质金属蛋白酶-9对经皮冠状动脉介入治疗后支架内再狭窄的诊断价值

目的 :探讨血清骨桥蛋白(OPN)及金属基质蛋白酶-9(MMP-9)水平变化对经皮冠状动脉介入治疗(PCI)后支架内再狭窄(ISR)的诊断价值。方法 :选择142例于我院接受PCI后复查冠状动脉造影检查的患者,根据冠状动脉造影结果分为再狭窄组(n=21)和无再狭窄组(n=121),复查冠状动脉造影时检测两组患者血清OPN、MMP-9等生化指标,比较两组患者临床资料、OPN及MMP-9等临床生化指标水平。结果:再狭窄组患者血清OPN及MMP-9水平显著高于无再狭窄组,差异有显著统计学意义(P0.001);Logistic多因素回归分析显示,OPN及MMP-9升高均是PCI后ISR发生的独立危险因素[优势比(OR)=3.034及OR=2.861,P0.01];在OPN及MMP-9预测ISR能力的受试者工作曲线(ROC)中,其曲线下面积为0.821及0.887,P0.001;当OPN及MMP-9分别取3.68 ng/ml和415.24 ng/ml时,联合检测可增加检测的敏感性(90.48%)和阴性预测价值(98.06%)。结论:PCI后患者血清OPN及MMP-9水平与ISR密切相关,联合检测血清OPN及MMP-9水平对ISR的发生具有一定的预测价值,尤其是其阴性预测价值。     

阿托伐他汀对心肌肥厚大鼠细胞外基质重塑的抑制作用

目的探讨阿托伐他汀对去甲肾上腺素诱导的心肌肥厚大鼠细胞外基质重塑的影响及其可能的机制.方法雄性SD大鼠随机分为三组(1)对照组,(2)去甲肾上腺素组[1.06 mg/(kg·d)×15 d],(3) 去甲肾上腺素+阿托伐他汀组[50 mg/(kg·d)×15 d].去甲肾上腺素ip,2次/d,15 d,建立心肌肥厚模型.应用超声心动图及病理学方法评价整体心肌肥厚及组织胶原表达.用逆转录-聚合酶链反应法(RT-PCR)及免疫组化检测细胞外基质调节因子-基质金属蛋白酶(MMP-9)及其生理性抑制剂(TIMP-1)和转化生长因子β1(TGF-β1)mRNA和蛋白表达.结果去甲肾上腺素组大鼠发生左心室肥厚及纤维化,胶原含量及MMP-9、TIMP-1和TGF-β-1蛋白、mRNA表达显著高于健康对照组(P<0.01).阿托伐他汀能减少心肌中总体胶原及Ⅰ、Ⅲ型胶原的合成及MMP-9、TGF-β-1表达(P<0.01).结论 MMP-9、TIMP-1和TGF-β-1与心肌肥厚大鼠的细胞外基质重塑有关.阿托伐他汀能有效防治心肌纤维化及细胞外基质重塑,这一效应与其降低心肌中高表达的MMP-9和TGF-β-1有关.     

雷帕霉素涂层支架预防血管内再狭窄的研究进展

如何防治冠状动脉介入治疗术后再狭窄形成已成为当今介入心脏学界面临的一大挑战 ,近年来的研究表明雷帕霉素涂层支架可有效预防再狭窄形成 ,为解决这一难题提供了新的治疗手段。本文就目前雷帕霉素涂层支架在临床防治再狭窄研究的最新进展作一综述。     

前列腺癌组织中血管生成与细胞外基质的相关性

目的探讨前列腺癌（PCa）组织中血管生成与细胞外基质（ECM）的相关性,及其与肿瘤生物学行为之间的关系。方法应用免疫组织化学LSAB法检测38例PCa患者癌组织中微血管密度（MVD）以及Ⅳ型胶原（COLⅣ）、纤维连接蛋白（FN）、层粘连蛋白（LN）等ECM。结果高分化癌组织中MVD）明显低于低分化和未分化者（P〈0．05）;有淋巴结转移的癌组织中MVD明显高于元转移者（P〈0．001）;高分化癌组织中COLⅣ、FN、LN呈连续型分布的百分率明显高于未分化者;有淋巴结转移者COLⅣ及FN呈连续型分布的百分率明显低于元转移者。COLⅣ、FN、LN呈连续型分布者的MVD均明显低于呈非连续型分布者,呈负相关。结论血管生成和ECM在PCa侵袭和转移过程中均起重要作用,两者关系密切,相互影响、相互作用。     

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell–matrix and cell–cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol (EtOH) exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, EtOH exposure generally increases perineuronal net components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD.     

Influence of Spironolactone on Matrix Metalloproteinase-2 in Acute Decompensated Heart Failure

Background

Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment.

Objective

Our aim was to test the influence of spironolactone in MMP2 levels.

Methods

Secondary analysis of a prospective, interventional study including 100 patients with ADHF. Fifty patients were non-randomly assigned to spironolactone (100 mg/day) plus standard ADHF therapy (spironolactone group) or standard ADHF therapy alone (control group).

Results

Spironolactone group patients were younger and had lower creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight did not differ between spironolactone and control groups. A trend towards a more pronounced decrease in MMP2 from baseline to day 3 was observed in the spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro BNP and weight also had a greater decrease in the spironolactone group. The proportion of patients with a decrease in MMP2 levels from baseline to day 3 was also likely to be greater in the spironolactone group (50% vs 66.7%), but without statistical significance. Correlations between MMP2, NT-pro BNP and weight variation were not statistically significant.

Conclusion

MMP2 levels are increased in ADHF. Patients treated with spironolactone may have a greater reduction in MMP2 levels.     

缬沙坦与安体舒通联合治疗对原发性高血压心肌细胞外基质重塑的影响

目的　研究缬沙坦与安体舒通联合治疗对原发性高血压 (EH)心肌细胞外基质重塑的影响。方法　选择 76例EH患者 ,随机分为两组 :X组 ,缬沙坦 80mg/d ,X A组 ,缬沙坦 80mg/d加安体舒通 2 0mg/d ,疗程 6月 ,应用放射免疫分析技术检测用药前后血清Ⅲ型前胶原 (PⅢP)、Ⅳ型前胶原 (PⅣP)、透明质酸 (HA)的含量变化 ,同时应用超声心动图记录左室结构及舒缩功能参数。结果　两组患者治疗 6月后血压均明显下降 (P <0 0 1) ,两组血压下降幅度比较无明显差异 (P >0 0 5 ) ,两组患者PⅢP、PⅣP、HA治疗 6月后均有下降 ,X A组下降明显 (与X组比较P <0 0 1) ,两组伴左室肥厚患者 (2 6例和 2 7例 )治疗 6月后室间隔厚度 (IVSD)、左室后壁厚度 (LPWD)、左室舒张末期内径 (LVIDD)、左室重量指数 (LVMI)较治疗前均有下降 ,但以X A组下降更明显 (与X组比较 ,P <0 0 5 ,P <0 0 1) ,同时 ,X A组左室舒张和收缩功能也得到明显改善 (P <0 0 5 ,P <0 0 1) ,两组均无明显不良反应发生。结论　缬沙坦与安体舒通联合治疗能更好地抑制肾素 -血管紧张素 -醛固酮系统 ,减轻心肌细胞外基质重塑 ,改善心室收缩和舒张功能 ,有利于提高EH患者的生活质量。     

冠状动脉旁路移植术后桥血管再狭窄治疗进展

冠状动脉旁路移植术后桥血管再狭窄问题值得临床关注,现主要对其相关治疗进展,包括药物治疗、基因治疗、再次手术治疗及介入治疗作一综述.     

Fas受体与冠状动脉支架内再狭窄研究进展

经皮冠状动脉介入治疗是治疗冠状动脉粥样硬化性心脏病的主要手段.然而,目前最重要的问题是经皮冠状动脉介入治疗术后进一步形成支架内再狭窄.凋亡与支架内再狭窄相关.Fas及其配体FasL是启动凋亡的相关分子.现综述Fas及其配体FasL与冠状动脉支架内再狭窄的相关研究.     

Reaggregation of Rat Dissociated Myenteric Plexus in Extracellular Matrix Gels

The aim of this study was to investigate the growth behavior of freshly dissociated myenteric plexus in a three-dimensional extracellular matrix (ECM) environment with and without stimulation of glial cell line-derived neurotrophic factor (GDNF). Therefore, cell suspensions of the dissected myenteric plexus of newborn rats were cultured in freshly prepared gels of commercially available mixtures of collagen, laminin, and hepatoglycans as a first step towards mimicking the natural environment of the myenteric plexus. The cultures were kept either in chemically defined serum-free medium alone or supplemented with GDNF. Cultures on polylysine-coated glass cover slips served as controls. Dissociated myenteric plexus grown on polylysine formed dense clusters of neurons with radially outgrowing nerve fibers, while the neurons cultured in the gel reaggregated to much smaller clusters. These contained, depending on the culture conditions, 2–10 neurons. The morphology of the network that was seen in the gels after a few days in vitro resembled very closely the in situ situation of the submucous plexus and the myenteric plexus in hypoganglionic children. Electron microscope investigations showed a high degree of organization with fiber bundles and vesicle-containing varicosities and growth cones. Independent of the method of culturing, GDNF obviously influenced the growth behavior of the dissociated plexus. The size of the ganglia was larger, and the secondary network denser when GDNF was supplemented. Moreover, the enteric neurons in the gel cultures tended to be larger in size when treated with GDNF. Three-dimensional cultures of dissociated myenteric plexus in an ECM gel might be a valuable tool towards the understanding of the formation of the enteric nervous system during development, especially considering pathological conditions such as Hirschsprungs disease or other dysganglionic diseases.