Proliferation of aortic smooth muscle cells and renin-angiotensin system in SHR rats

目的：探讨ＳＨＲ大鼠主动脉平滑肌细胞（ＡＳＭＣ）异常增殖和肾素血管紧张素系统（ＲＡＳ）的关系．方法：测定血管紧张素Ｉ（Ａｎｇ）、卡托普利（Ｃａｐ）、沙拉新（Ｓａｒ）对培养的ＳＨＲ、ＷＫＹＡＳＭＣ增殖和Ａｎｇ、血管紧张素转化酶（ＡＣＥ）的影响．结果：Ａｎｇ在２％血清培养基中可刺激ＳＨＲＡＳＭＣ增生．ＳＨＲＡＳＭＣ分裂增殖能力比ＷＫＹ强，ＳＨＲＡＳＭＣＲＡＳ处于高功能状态．Ｃａｐ长期（４周）干预显著抑制ＳＨＲＡＳＭＣ异常增殖和Ａｎｇ、ＡＣＥ活性，Ｓａｒ长期干预同样抑制ＳＨＲＡＳＭＣ的增殖和ＡＣＥ活性，但Ａｎｇ水平反而升高．Ｃａｐ短期（２４小时）干预不影响两种大鼠ＡＳＭＣＲＡＳ．结论：Ｃａｐ和Ｓａｒ长期干预通过减少ＳＨＲＡＳＭＣＡｎｇ生成或阻断Ａｎｇ和特异受体结合，抑制其异常增殖．     

雷公藤治疗系统性红斑狼疮免疫机制的研究

目的：探讨雷公藤治疗系统性红斑狼疮的免疫作用机制。方法：用系统性红斑狼疮（ＳＬＥ）的外周血单个核细胞（ＰＢＭＣ）体外培养观察雷公藤对于ＳＬＥ的Ｔ,Ｂ细胞功能的影响。结果;雷公藤不仅能抑制ＳＬＥ病人ＰＢＭＣ对ＰＨＡ诱导的增殖反应,也能抑制ＳＬＥ病人活化Ｂ细胞的自发增殖以及ＳＡＣ诱导的静止期Ｂ细胞的增殖反应。另外雷公藤还能明显的抑制ＳＬＥ病人ＰＢＭＣ的自发性ＩｇＧ分泌以及ｒ－ＩＬ２诱导的ＰＢＭＣ的Ｉｇ     

重组人可溶性血管内皮细胞生长抑制因子的抗新生血管形成活性研究

管内皮细胞生长抑制因子（Ｖascular Endothelial Growth Inhibitor,ＶＥＧＩ）是从人脐静脉内皮细胞（ＨＵＶＥＣ）cＤＮＡ文库筛选到的一个ＴＮＦ超家庭新成员,为研究重组可溶性人ＶＥＧＩ对新生血管形成抑制活性,检测了重组可溶性人ＶＥＧＩ对建株人脐静脉内皮细胞（ＥＣＶ３０４）增殖抑制活性以及对兔角膜诱生血管、鸡胚尿囊膜（ＣＡＭ）血管的抑制活性。表明可溶性人ＶＥＧＩ可以直接抑制ＥＣＶ３０４内皮细胞的增殖,抑制兔角膜诱生血管、ＣＡＭ血管形成。ＶＥＧＩ是一种新的血管内皮细胞生长抑制因子,强烈抑制新生血管形成,有望应用于肿瘤的治疗。     

培养的大鼠主动脉平滑肌细胞表达糖基化终产物受体和地尔硫Zh…

目的：探讨培养的主动脉平滑肌细胞（ＡＳＭＣ）上是否表达糖基化终产物（ＡＧＥＰ）高亲性受体和地尔硫Ｚｈｕｏ对ＡＧＥＰ升高胞浆游离钙的抑制。方法：用放射配基结合方法研究ＡＳＭＣ与ＡＧＥＰ的相互作用；用钙离子荧光指示剂Ｆｕｒａ２－ＡＭ测定ＡＳＭＣ胞浆游离钙。结果：ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达，其解离常数为６５．３±１．５ｍｏｌ·Ｌ＾－１，最大结合容量１．５７±０．０４ｎｍｏｌ／ｇ细胞蛋白；通过该     

海洋硫酸多糖DPS对大鼠血管平滑肌细胞增殖的影响

本文采用碱性成纤维细胞生长因子（ｂＦＧＦ）和白介素－１（ＩＬ－１）氘诱导的大鼠血管平滑肌细胞（ＶＳＭＣ）增殖模型,以ＭＴＴ法观察了海洋硫酸多糖ＤＰＳ对ＶＳＭＣ增殖的影响。大鼠血管平滑肌细胞在ＤＰＳ浓度为０．００１μｇ／ｍｌ～１００μｇ／ｍｌ的２液中孵育２４ｈ后,分别加入ｂＦＧＦ（５０ｍｇ／ｍｌ）或ＩＬ－１（５０Ｕ／ＭＬ）再孵育２４ｈ,用ＭＴＴ法测定海洋硫酸多糖ＤＰＳ对ＶＳＭＣ增殖的影响。结果表明,     

五种海藻多糖体外抗血小板聚集作用的观察

本文主要对海带（Ｌａｍｉｎａｒｉａ ｊａｐｅｎｉｏａ Ａｒｅｓｃｈ）、鼠尾藻［Ｓａｒｇａｓｓｕｍ ｔｈｕｎｂｅｒｇｉｌ（Ｍｅｒｔ）　ｏ＇Ｋｕｎｔｇｅ］、萱藻［Ｓｃｙｔｏｓｉｐｈｏｎ Ｌｏｍｅｎｔａｒｕｓ（Ｌｙｎｇｂ）Ｊ．Ａｇ］、石莼［Ｕｌｖａ．ｌａｃｔｕｃａｌ］、刚毛［ｃｌａｄｏｐｈｏｒａ ｋｕｔｚｉｎｇ］５种海藻多糖的硫酸基含量以及体外抗血小板聚集作用进行了观察。结果发现,萱藻多糖的硫酸基含量及抗血小板聚集作用显著高于其他海藻多糖,其他依次为鼠尾藻、海带、石莼。刚毛多糖的抗血小板聚集的作用不显著。５种海藻多糖的抗凝血活性与其硫酸基含量是显著正相关。     

Expression of receptor for advanced glycosylation end products(AGEP)and inhibition of AGEP-induced cytosolic calcium elevationbydiltiazeminculturedrataorticsmoothmusclecels

目的：探讨培养的主动脉平滑肌细胞（ＡＳＭＣ）上是否表达糖基化终产物（ＡＧＥＰ）高亲性受体和地尔硫对ＡＧＥＰ升高胞浆游离钙的抑制．方法：用放射配基结合方法研究ＡＳＭＣ与ＡＧＥＰ的相互作用；用钙离子荧光指示剂Ｆｕｒａ２ＡＭ测定ＡＳＭＣ胞浆游离钙．结果：ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达，其解离常数为６５３±１５ｎｍｏｌ·Ｌ－１，最大结合容量１５７±００４ｎｍｏｌ／ｇ细胞蛋白；通过该受体介导，平滑肌细胞可内化、代谢ＡＧＥＰ．ＡＧＥＰ使胞浆游离钙呈浓度依赖性升高；地尔硫呈时间、浓度依赖性抑制此效应．结论：大鼠ＡＳＭＣ上有ＡＧＥＰ高亲和性受体表达；地尔硫可抑制ＡＧＥＰ介导的胞浆游离钙升高．     

自发性高血压大鼠主动脉平滑肌细胞异常增殖和局部肾素—血管？…

目的：探讨ＳＨＲ大鼠主动脉平滑肌细胞（ＡＳＭＣ）异常增殖和肾素－血管紧张素系统９ＲＡＳ）的关系。方法：测定血管紧张素Ⅱ（Ａｎｇ）、卡托普利（Ｃａｐ）、沙拉新（Ｓａｒ）对培养的ＳＨＲ、ＷＫＹ ＡＳＭＣ增殖的Ａｎｇ、血管紧张素转化酶（ＡＣＥ）的影响，结果：Ａｎｇ在２％血清培养基中可刺激ＳＨＲ ＡＳＭＣ增生，ＳＨＲ ＡＳＭＣ分裂增殖能力比ＷＫＹ强，ＳＨＲ ＡＳＭＣ ＲＡＳ处于高功能状态。Ｃａｐ长期（４周     

彗星试验检测7种化合物对外周血淋巴细胞DNA的损伤

目的：检测过氧化氢（Ｈ２Ｏ２）、甲磺酸乙酯（ＥＭＳ）、丝裂霉素Ｃ（ＭＭＣ）、二甲基亚硝胺（ＤＭＮＡ）、苯并（ａ）芘（ＢａＰ）、２－氨基Ｗｕ（２－ＡＦ）和环磷酰胺（ＣＰ）诱发小鼠、大鼠及人外周血淋巴细胞ＤＮＡ单链断裂。方法：体外单细胞微量凝胶碱性电泳试验（慧星试验）。结果：除ＥＭＳ０．９７ｍｍｏｌ·Ｌ＾－１在小鼠淋巴细胞，ＭＭＣ３０μｍｏｌ·Ｌ＾－１在小鼠、人淋巴细胞中呈阴性外，其余均为阳性。最低可     

丙泊酚抑制去甲肾上腺素诱导大鼠肺动脉平滑肌细胞内游离钙浓度升高作用的机理

用荧光分光光度法及同位素放射免疫分析法检测丙泊酚（３０－３００μｍｏｌ·Ｌ－１）影响大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）内游离钙离子浓度（［Ｃａ２＋］ｉ）与肌醇－１,４,５－三磷酸（ＩＰ３）合成作用,以探讨丙泊酚舒张肺动脉平滑肌的作用机理．结果表明,与丙泊酚共同培养７２ｈ,对ＰＡＳＭＣ［Ｃａ２＋］ｉ基础水平无明显影响,但可浓度依赖性抑制去甲肾上腺素（ＮＥ３μｍｏｌ·Ｌ－１）引起的［Ｃａ２＋］ｉ升高作用;当细胞外液无钙或存在钙通道阻滞剂维拉帕米（３０μｍｏｌ·Ｌ－１）时,丙泊酚抑制ＮＥ升高［Ｃａ２＋］ｉ作用被增强;丙泊酚还可浓度依赖性抑制ＮＥ促进ＩＰ３合成作用．结果提示丙泊酚舒张血管平滑肌作用与抑制ＩＰ３介导的细胞内钙释放密切相关．     

Inhibition of cultured bovine aortic smooth muscle cell proliferation by colominic acid

Colominic acid (CA) is an alpha2,8-linked polymer of sialic acid, originally isolated from capsular Escherichia coli K1. Since inhibition of arterial smooth muscle cell hyperplasia is one of the effective strategies to prevent atherosclerosis, we investigated the effect of CA, purified as an alpha2,8-linked homopolymer of N-acetylneuraminic acid, on the proliferation of bovine aortic smooth muscle cells in culture. The results demonstrate that CA inhibits the proliferation of the cells without nonspecific cell damage. Sulfation did not modify the inhibitory effect of CA. Specifically, the inhibitory effect of sulfated CA was almost equal to that of CA in vascular smooth muscle cell proliferation. On the other hand, it was suggested that the inhibition of the proliferation by CA is in a degree similar to that by heparin but weaker than that by sodium/calcium-spirulans, known sulfated polysaccharides as the potent inhibitor of vascular smooth muscle cells. The present data suggest that CA with or without sulfate groups can be an origin of beneficial agents that prevents atherosclerosis through a moderate inhibition of arterial smooth muscle cell proliferation.     

Platelet function and signaling in diabetes mellitus

Diabetes mellitus is associated with the accelerated development of vascular disease and there is evidence that platelets actively contribute to this process. Certainly, platelets are able to modulate the function of endothelial and vascular smooth muscle cells via the direct release of growth factors and pro-inflammatory chemokines but also via the production of microparticles which function as a transcellular delivery system for micro RNAs. This article reviews the intracellular signaling mechanisms underlying the increased activation of diabetic platelets and the involvement of platelets in atherothrombosis development.     

Adenosine agonists for the prevention of restenosis?

Balloon angioplasty involves the simultaneous activation of platelets and neutrophils. Activated platelets release mitogenic substances that cause smooth muscle cell proliferation and thereby contribute to restenosis. Activated neutrophils activate platelets and activated platelets activate neutrophils. Therefore the simultaneous activation of both cell types may be responsible for the exaggerated repair mechanisms resulting in restenosis of coronary blood vessels. Adenosine inhibits neutrophil activation, platelet activation and smooth muscle cell proliferation and stimulates endothelial cell proliferation predominantly through activation of A2A-receptors. Adenosine and A2A-selective agonists may be useful in the prevention of restenosis following balloon angioplasty.     

Effect of paclitaxel and mesenchymal stem cells seeding on ex vivo vascular endothelial repair and smooth muscle cells growth

Late thrombosis and neointima proliferation after paclitaxel-eluting stents implanting may be related to delayed endothelial cells (ECs) regeneration. This study was to investigate whether mesenchymal stem cells (MSCs) seeding can accelerate endothelial repair and attenuate late smooth muscle cells (SMCs) proliferation after paclitaxel intervention. An ex vivo model of endothelium repair was developed in which rabbit smooth muscle cells were inoculated in the upper chamber and rabbit endothelial cells/human mesenchymal stem cells in the lower chamber of a co-culture system. Paclitaxel (10 nmol/L, 20 min) inhibited smooth muscle cell growth of the confluent endothelial cell group during the observed period. However, increased smooth muscle cells growth was observed in the proliferative endothelial cells group 10 days after paclitaxel intervention. Mesenchymal stem cell seeding inhibited late smooth muscle cell growth incompatible with the effect of proliferative endothelial cells. However, no inhibition on smooth muscle cell growth was observed with mesenchymal stem cell seeding in comparison to the effect of confluent endothelial cells. No vWF but Flk-1 protein was observed in the 25.71% of mesenchymal stem cells after having been co-cultured with rabbit endothelial cells for 5 days. These results indicate that late smooth muscle cell proliferation is closely related to the delayed endothelial cells regeneration after paclitaxel application. Mesenchymal stem cell seeding partly attenuates the late smooth muscle cell proliferation. Mesenchymal stem cells co-cultured with mature endothelial cells have the ability to differentiate toward endothelial cells.     

吉非替尼通过抑制EGFR/Akt信号通路特异性抑制平滑肌细胞增殖

目的:探讨表皮生长因子受体 (epidermal growth factor receptor,EGFR)抑制剂吉非替尼对平滑肌细胞(smooth muscle cells, VSMC) 和内皮细胞 (ndothelial cells, EC) 增殖的影响,以及对EGFR和Akt蛋白表达及磷酸化的影响。方法:将大鼠VSMC及EC置于含0.01~10 μmol·L的吉非替尼的培养基中培养24~72 h,以MTT法测定细胞增殖的抑制率。Western blot检测EGFR及磷酸化EGFR(p-EGFR)、Akt及磷酸化Akt(p-Akt)蛋白水平。结果:MTT结果显示,吉非替尼抑制VSMC增殖呈时间和浓度依赖性,而吉非替尼对EC增殖的抑制作用明显低于紫杉醇;Western blot结果显示VSMC中EGFR(1.07±0.13)表达与EC(0.58±0.05)相比明显增多(P<0.01),而吉非替尼可明显抑制VSMC中EGFR及Akt蛋白的磷酸化。结论:类似紫于杉醇,吉非替尼可抑制VSMC增殖,而对EC的细胞毒性作用明显低于紫杉醇,其机制可能是通过抑制EGFR及Akt蛋白磷酸化来实现的。     

动脉粥样硬化血管内皮分泌功能失调与平滑肌细胞增殖

血管内皮细胞和平滑肌细胞是血管壁两种主要细胞,两者在结构上和功能上有着密切的关系,动脉粥样硬化的发生源于循环因子和血管壁细胞间的相互作用,内皮细胞损伤等所导致的分泌功能失调和平滑肌细胞的异常增殖而引起的血管腔狭窄和痉挛是动脉粥样硬化等多种血管疾病发生发展的共同病理基础。本文从动脉粥样硬化病理状态下血管内皮分泌的生长因子、细胞因子、血管活性物质对平滑肌细胞增殖影响的最新研究进展做一综述。     

THE THROMBIN RECEPTOR

1. The thrombin receptor has now been cloned and found to be a member of the G-protein-coupled seven-transmembrane domain receptor family. 2. The receptor has been detected directly in platelets, endothelial cells and smooth muscle cells and studies using receptor-derived peptides have demonstrated that this receptor may be the one responsible for many of the actions of thrombin in platelets, endothelial cells, smooth muscle cells, fibroblasts, mesangial cells and neural cells. 3. The receptor appears to be activated by the novel mechanism of cleavage by thrombin to yield a new N-terminus which then interacts with the receptor as a tethered ligand to initiate cell activation.     

Interactions between Cultured Bovine Arterial Endothelial and Smooth Muscle Cells: Effects of Injury on the Release of Growth Stimulating and Growth Inhibiting Substances

Abstract: Dimethylsulfoxide-soluble particles (DSP) from cigarette smoke and ultraviolet light caused a low degree (cell death < 30%) and high degree (cell death 60-90%) injury to bovine arterial endothelial cells and smooth muscle cells in culture. Conditioned medium from low degree injured endothelial cells and smooth muscle cells generally inhibited DNA synthesis in new smooth muscle cells or endothelial cells while high degree injury increased DNA synthesis in new cells. Specifically, the growth stimulating activity from endothelial cells was decreased after low degree injury but increased after high degree. UV light released more growth stimulating substances from smooth muscle cells after both low and high degree injury. The release of growth inhibiting substances was dependent on both cell kind and degree of injury. In co-culture low and high degree DSP injury to endothelial cells inhibited smooth muscle cell proliferation, which was in contrast to the effect of conditioned medium from high degree injured endothelial cells. Conditioned medium from endothelial cells treated with LDL and glucose inhibited DNA synthesis in smooth muscle cells. It is concluded that injury to endothelial cells or smooth muscle cells will modify the release of growth inhibiting and growth stimulating activity and that this release will depend on cell kind as well as degree and kind of the injurious stimulus.     

Biological activities of exogenous polysaccharides via controlling endogenous proteoglycan metabolism in vascular endothelial cells

Proteoglycan contains glycosmainoglycans, which are endogenous sulfated polysaccharides, in the molecule. The metabolism of proteoglycans regulates cell behavior and cellular events. It is possible that exogenous polysaccharide-related molecules exhibit their biological activities by two mechanisms. One is the interaction with cells and the other is the interaction with growth factors/cytokines that regulate proteoglycans. In this review, we describe sodium spirulan, a sulfated polysaccharide obtained from a hot-water extract of the blue-green alga Spirulina platensis, as an exogenous polysaccharide that stimulates the release of proteoglycans from vascular endothelial cells. Factors that regulate endothelial proteoglycan metabolism are also being described as possible target molecules of exogenous polysaccharides. Further research is required to obtain exogenous polysaccharide-related molecules that exhibit useful biological activities through controlling endothelial proteoglycan metabolism for protection against vascular lesions such as atheroslcerosis.     

Interactions between cultured bovine arterial endothelial and smooth muscle cells: effects of injury on the release of growth stimulating and growth inhibiting substances.

Dimethylsulfoxide-soluble particles (DSP) from cigarette smoke and ultraviolet light caused a low degree (cell death less than 30%) and high degree (cell death 60-90%) injury to bovine arterial endothelial cells and smooth muscle cells in culture. Conditioned medium from low degree injured endothelial cells and smooth muscle cells generally inhibited DNA synthesis in new smooth muscle cells or endothelial cells while high degree injury increased DNA synthesis in new cells. Specifically, the growth stimulating activity from endothelial cells was decreased after low degree injury but increased after high degree. UV light released more growth stimulating substances from smooth muscle cells after both low and high degree injury. The release of growth inhibiting substances was dependent on both cell kind and degree of injury. In co-culture low and high degree DSP injury to endothelial cells inhibited smooth muscle cell proliferation, which was in contrast to the effect of conditioned medium from high degree injured endothelial cells. Conditioned medium from endothelial cells treated with LDL and glucose inhibited DNA synthesis in smooth muscle cells. It is concluded that injury to endothelial cells or smooth muscle cells will modify the release of growth inhibiting and growth stimulating activity and that this release will depend on cell kind as well as degree and kind of the injurious stimulus.