钙稳态失衡在内皮损伤后血管平滑肌增生中的作用

目的探讨内皮剥脱后血管平滑肌细胞钙稳态的变化及其在内皮损伤诱导血管平滑肌细胞的增殖中的作用。方法在大鼠球囊内皮剥脱模型上，用３Ｈ－胸腺嘧啶核苷和３Ｈ－亮氨酸掺入及４５Ｃａ转运的方法。结果内皮损伤可导致血管平滑肌细胞增殖、内膜增厚；血管平滑肌细胞钙内流增多，剥脱后３天时为４．１２±０．２８、对照组为３；２８±０．１４ｎｍｏｌ／×１０６细胞（Ｐ＜０．０５）；１０天时为４．０９±０．２１、对照组３．３１±０．０９ｎｍｏｌ／×１０６细胞，（Ｐ＜０．０１）、钙外移减少、钙含量升高（剥脱后３天时为９９５±５４、对照组为６９５±３３ｎｍｏｌ／×１０６细胞（Ｐ＜０．０１）；１０天时为１０２２±９４对照组、７０９±３２ｎｍｏｌ／×１０６细胞（Ｐ＜０．０１））、肌浆网和线粒体钙摄取功能增强；应用钙通道阻断剂治疗可以调整内皮剥脱后血管平滑肌细胞的钙稳态失衡，还可以抑制内皮损伤诱导的血管平滑肌细胞增殖。结论钙稳态失衡可能是内皮损伤引起血管平滑肌细胞增殖的细胞学机制之一。     

降钙素基因相关肽对大鼠主动脉内皮剥脱的保护作用

为研究降钙素基因相关肽在防止动脉内膜损伤后平滑肌细胞增殖所致再狭窄中的作用机制，采用内皮剥脱、血管条灌流和放射免疫测定法测定了环磷一酸尿苷、降钙素基因相关肽和内皮素水平。结果发现，内皮剥脱后两周，血浆及主动脉组织降钙素基因相关肽含量增加（前者对照组为9．2±1．7，去内皮组为14．1±2．0ng／L；后者对照组为7．4±1．4，去内皮组为12．2±2．0ng／g）。应用外源性降钙素基因相关肽（25μg/Kg）可明显改善损伤血管对乙酰胆碱的内皮依赖性舒张反应；促进去内皮血管壁一氧化氮的合成；增加主动脉组织内cGMP的含量（对照组4．4±0．5，去内皮组2．0±0．5，降钙素基因相关肽组3．3±0．5ng/g；P＜0．01），减少内皮素的生成（P＜0．01），抑制损伤部位的内膜过度憎生（P＜0．01）．提示外源性降钙素基因相关肽可通过促进内皮的修复、抑制内膜的过度增殖而防止剥脱血管的再狭窄。     

辛伐他汀降脂治疗对血管内皮依赖性舒张功能的影响

目的研究辛伐他汀对原发性高胆固醇血症患者血管内皮依赖性舒张功能的影响。方法采用高分辨超声技术，对２５例原发性高胆固醇血症患者降脂前后和２５例血浆胆固醇水平正常的对照者的血管内皮依赖性舒张功能进行检测。结果发现原发性高胆固醇血症组肱动脉血流介导性舒张较正常组明显减弱（３．５％±２．８％和１４．５％±３．４％，Ｐ＜０．００１），而二组对硝酸甘油的反应无显著性差异（２０．５％±７．２％比２２．９％±４．３％，Ｐ＝０．４９）。２５例原发性高胆固醇血症患者服用辛伐他汀５～１０ｍｇ治疗３．８±０．８月后，血浆总胆固醇从６．３１±０．７０ｍｍｏｌ／Ｌ降至５．０６±０．６３ｍｍｏｌ／Ｌ，同时肱动脉内皮依赖性舒张较治疗前明显改善（１０．０±３．２％比３．５±２．８％，Ｐ＜０．００１），而治疗前后肱动脉对硝酸甘油的反应无显著性改变。结论原发性高胆固醇血症患者存在血管内皮依赖性舒张功能障碍；经辛伐他汀降胆固醇治疗后，受损的血管内皮依赖性舒张功能得到明显改善     

老年高血压患者阿托伐他汀治疗前后血清C反应蛋白水平变化及意义

将78例老年高血压患者随机分为对照组和阿托伐他汀组（治疗组）。两组均常规治疗，在此基础上治疗组每晚睡前服用阿托伐他汀10mg，共8周。检测两组治疗前后血清C反应蛋白（CRP）、血压、血脂和血管内皮依赖性舒张功能变化。结果两组降压效果无显著差异；治疗后对照组血脂、血清CRP和内皮依赖性舒张功能无明显变化，而治疗组血脂、血清CRP明显降低，血管内皮依赖性舒张功能明显改善（P〈0．01）。表明阿托伐他汀除鼻有降脂作用外。还具有减辑血管炎症反应、改善内应功能的作用．     

血管损伤影响离体平滑肌细胞增殖与钙稳态有关

本实验采用球囊剥脱术在体损伤血管，于术后３天和１０天取出血管做平滑肌细胞培养。结果发现，血管损伤后血管平滑肌细胞增殖活性显著增加，ＤＮＡ和蛋白质合成加速，细胞数目增多。在血管平滑肌细胞增殖过程中，钙内流增加，胞内钙含量升高。应用１０μｍｏｌ·Ｌ￣（－１）异搏定不但对钙稳态变化有一定的抑制作用，而且还对血管损伤诱导的平滑肌细胞增殖有抑制作用。这些结果提示血管损伤可致血管平滑肌细胞增殖；钙稳态失衡可能是血管损伤诱导血管平滑肌细胞增殖的细胞学机制之一。     

阿托伐他汀对高血压患者血管内皮功能的影响

目的探讨高血压患者应用阿托伐他汀治疗后对血管内皮舒张功能、C反应蛋白(CRP)、纤维蛋白原(FIB)、内皮素(ET)的影响.方法137例高血压患者随机分成阿托伐他汀治疗组(阿托伐他汀10 mg/d qd,观察组69例)及常规治疗组(对照组68例),比较治疗12周前后应用超声检测肱动脉流量介导性扩张的血管内皮舒张功能及C反应蛋白(CRP)、纤维蛋白原(FIB)、内皮素(ET)水平的变化.结果观察组和对照组治疗前与治疗12周后比较,血管内皮舒张功能均有显著改善(P＜0.01和P＜0.05);治疗后两组间比较,血管内皮舒张功能(FMD7.95±0.87 vs 5.20±0.82;GTN12.12±5.11vs 10.38±5.10)及C反应蛋白(CRP3.14±0.53 vs 7.42±0.42)、纤维蛋白原(FIB236±103 vs 402±112)、内皮素(ET3.41±1.94 vs 4.51±2.70)水平有显著差异(P＜0.05).结论高血压患者应用阿托伐他汀治疗12周后可进一步改善内皮依赖性血管舒张功能,同时可减轻炎症反应,纤溶活性及血浆内皮素均有不同程度的改善.     

阿托伐他汀对高血压患者血管内皮功能的影响

目的探讨高血压患者应用阿托伐他汀治疗后对血管内皮舒张功能、C反应蛋白(CRP)、纤维蛋白原(FIB)、内皮素(ET)的影响。方法137例高血压患者随机分成阿托伐他汀治疗组(阿托伐他汀10mg/dqd,观察组69例)及常规治疗组(对照组68例),比较治疗12周前后应用超声检测肱动脉流量介导性扩张的血管内皮舒张功能及C反应蛋白(CRP)、纤维蛋白原(FIB)、内皮素(ET)水平的变化。结果观察组和对照组治疗前与治疗12周后比较,血管内皮舒张功能均有显著改善(P<0.01和P<0.05);治疗后两组间比较,血管内皮舒张功能(FMD:7.95±0.87vs5.20±0.82;GTN:12.12±5.11vs10.38±5.10)及C反应蛋白(CRP:3.14±0.53vs7.42±0.42)、纤维蛋白原(FIB:236±103vs402±112)、内皮素(ET:3.41±1.94vs4.51±2.70)水平有显著差异(P<0.05)。结论高血压患者应用阿托伐他汀治疗12周后可进一步改善内皮依赖性血管舒张功能,同时可减轻炎症反应,纤溶活性及血浆内皮素均有不同程度的改善。     

抗氧化剂对脂质过氧化内皮细胞表达细胞粘附分子的影响

为研究一氧化氮合酶抑制剂左旋硝基精氨酸诱导的肺动脉高压大鼠各部位离体血管环对多巴胺－ １ 受体反应性的影响，采用大鼠肺动脉、肠系膜动脉和肾动脉离体血管标本，在去甲肾上腺素收缩血管后，用多巴胺－ １ 受体选择性激动剂非诺多泮使血管舒张，所有实验在吲哚美辛（１０ μｍｏｌＬ） 和普萘洛尔（３ μｍｏｌＬ） 存在下进行。左旋硝基精氨酸组大鼠各动脉对非诺多泮的反应性均有不同程度的降低，以肺动脉最明显，最大舒张占预收缩的百分比为４５．５％ ±４．１％ ，低于对照组的９７．３ ％ ±１０ ．６ ％（ Ｐ＜ ０．０１）；亲合常数为２０４２ ±２２１，低于对照组的４２７４ ．２±５１２（Ｐ＜ ０．０１） ，接近对照组的去内皮水平。肠系膜动脉和肾动脉对非诺多泮的反应性亦有下降，但下降程度明显低于肺动脉。结果提示，内皮依赖性受体介导多巴胺－ １ 的舒张效应降低是左旋硝基精氨酸形成肺动脉高压的因素之一。     

洛伐他汀对同型半胱氨酸硫内酯所玫大鼠离体胸主动脉内皮损伤的保护作用

目的观察洛伐他汀对同型半胱氨酸硫内酯所致大鼠离体胸主动脉内皮损伤的保护作用并探讨其相关机制。方法用同型半胱氨酸硫内酯与大鼠离体胸主动脉血管环共孵育90min诱导血管内皮损伤，检测血管内皮依赖性、非内皮依赖性舒张反应以及血管组织生物化学指标，观察洛伐他汀对同型半胱氨酸硫内酯诱导的血管内皮功能损伤的影响。结果血管环与同型半胱氨酸硫内酯孵育90min后，乙酰胆碱诱导的内皮依赖性舒张反应明显降低，而硝普钠引起的非内皮依赖性舒张反应无明显改变；血管组织中丙二醛浓度显著增加，超氧化物歧化酶活性下降，一氧化氮含量减少，与正常对照组相比差异有显著性（P〈0．05）；给予洛伐他汀10、20和40μmol／L可明显减轻同型半胱氨酸硫内酯对离体胸主动脉血管环内皮依赖性舒张反应的损伤。使Emax从39．72％&#177;1．91％分别升至54、84％&#177;1．89％、66．25％&#177;1．93％和80．12％&#177;1．32％，半数有效浓度从230．45&#177;13．42nmol／L分别降至145．34&#177;13．19nmol／L、126．93&#177;12．91nmol／L和109．16&#177;14．20nmol／L，一氧化氮水平从0．26&#177;0．04mmol／g分别升至0．51&#177;0．05、0．67&#177;0．03和0．88&#177;0．04mmol／g，同时血管组织中丙二醛含量明显降低，超氧化物歧化酶活性升高。与同型半胱氨酸硫内酯损伤组相比差异均有显著性（P〈0．05或P〈0．01）。超氧化物歧化酶、N-乙酰半胱氨酸、左旋精氨酸也有和洛伐他汀相类似的抗同型半胱氨酸硫内酯损伤作用，而L-N-硝基精氨酸甲酯可拮抗洛伐他汀的抗同型半胱氨酸硫内酯的损伤作用。结论洛伐他汀能拮抗同型半胱氨酸硫内酯对血管内皮功能的损伤作用，其机制可能与抑制氧化应激、保护血管内皮的一氧化氮合成与释放有关。     

冠心病患者合并心衰时血管内皮功能的变化及氯沙坦治疗的影响

目的:了解慢性充血性心衰(CHF)时血管内皮功能变化及氯沙坦对冠心病CHF患者血管内皮功能的影响。方法:比较50例冠心病CHF患者、46例冠心病患者以及52例正常对照组患者的血管内皮功能,以内皮依赖性血管舒张反应和血浆内皮素(ET-1)和vWF水平评价内皮功能。25例CHF患者采用氯沙坦治疗12周后评价内皮功能变化。结果:CHF组内皮依赖性血管扩张(△D%)5.42±4.17程度低于对照组12.01±4.04%和CAD组7.74±3.15%(P<0.01);CHF组血浆ET-1值60.03±17.49pg/ml较对照组44.24±8.92pg/ml、CAD组46.91±14.42pg/ml值明显增高(P<0.01),CHF组vWF值171.24±46.95%与CAD组168.69±46.92%均较对照组132.0±37.47%增高(P>0.01)。CHF患者通过氯沙坦治疗后,内皮依赖性血管扩张(△D%)明显增加(P<0.01),血浆ET-1、vWF水平下降(P<0.05)。结论:CHF时血管内皮功能障碍加重,氯沙坦治疗能有效改善其血管内皮功能。     

Acute cellular damage in medial smooth muscle cells following experimental coronary angioplasty in Dog. Damage of cytoskeleton and apoptosis

Summary The purpose of the present study was to investigate the responses of the cytoskeleton and the presence of apoptosis following acute damage of medial smooth muscle cells after percutaneous transluminal coronary angioplasty (PTCA). We killed 20 dogs, 4h and 4 days after PTCA (n=10 in each group). Ten dogs without PTCA were used as controls. PTCA was achieved by inflating balloon catheters two times, for 60s each time, to 150 PSI, followed by a 60-s deflation. The coronary artery obtained from each dog was fixed in 10% formalin neutral buffer solution. The response of the cytoskeleton was studied immunohistochemically, using monoclonal antibodies against α-smooth muscle actin, vimentin, and β-tubulin. Proliferation was determined by proliferating cell nuclear antigen (PCNA), and DNA fragmentation indicating apoptosis was determined by in situ nick end labeling. Four h after PTCA, endothelial denudation, microscopic mural thrombi, rupture of the internal elastic membrane, medial tear, and stretched smooth muscle cells with nuclei were found at the PTCA site. An immunohistochemical study revealed diffuse reduction or defective immunoreactivity in each cytoskeleton of medial smooth muscle cells, 4h after PTCA. The extent of positive immunoreactivity in the media decreased to 45±11% in α-smooth muscle actin (control value, 80±10%), 9±8% in vimentin (control value, 83±9%), and 10±7% in β-tubulin (control value, 75±8%). The decrease was more significant in vimentin and β-tubulin than in α-smooth muscle actin. Four days after PTCA, the features were diffuse cell death and the focal proliferation of medial cells, as well as macroscopic intramural thrombi. The extent of positive immunoreactivity in the media was 15±9% in α-smooth muscle actin, 13±7% in vimentin, and 14±11% in β-tubulin. There were no smooth muscle cells with positive PCNA (0%) in the control and 4-h groups, but 4 days after PTCA the percentage was 19±4%. In situ nick end labeling showed DNA fragmentation in the nuclei of medial smooth muscle cells at a rate of 15±5% 4h after PTCA and at 8±6% 4 days after PTCA, compared with 0% in the control. We concluded that severe damage of the cytoskeleton and medial smooth muscle cell death were induced immediately after PTCA, followed by proliferation of smooth muscle cells. Apoptosis may be partially involved in the death of smooth muscle cells, in addition to necrosis. Damage to the cytoskeleton and apoptosis may play an important role in the pathogenesis of acute lesions and the proliferation of smooth muscle cells after PTCA.     

球囊血管损伤后平滑肌细胞凋亡对内膜增殖的影响

目的检测球囊损伤动脉血管后,平滑肌细胞的凋亡及血管紧张素Ⅱ受体阻断剂对其影响,探讨血管平滑肌细胞增殖机制。方法40只雄性Sprague-Dawley大鼠,随机分为1组(对照组):假手术组;2组:手术后7d组;3组:手术后14d组;4组(氯沙坦组):手术+氯沙坦14d组,行球囊血管损伤术。采用原位末端标记法(TUNEL法)及组织学方法结合图像分析,检测各组血管平滑肌细胞凋亡和内膜增生情况。结果TUNEL阳性细胞率,氯沙坦组(41.5±9.7)%明显高于2组(28.3±5.8)%和3组(21.1±8.6)%,差异有显著性(P<0.01)。氯沙坦组内膜增生(38.8±10.1)μm明显轻于3组(93.4±22.2)μm,差异有显著性(P<0.01)。结论血管平滑肌细胞凋亡不足,可能是球囊损伤后血管内膜增殖的机制之一。血管紧张素Ⅱ受体1(AT1)阻断剂氯沙坦能增加血管平滑肌细胞凋亡。     

Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery.

BACKGROUND. We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity. METHODS AND RESULTS. New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone. CONCLUSIONS. The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.     

Organ culture of human coronary artery following balloon angioplasty

Intimal smooth muscle cell proliferation is the primary cause of restenosis following balloon angioplasty. Its underlying basis and progression remain unclear. The authors developed an organ culture of human coronary artery subjected to balloon angioplasty in order to investigate the cellular and molecular basis of intimal proliferation in a preparation that maintained the anatomic relationships of the vessel wall. Artery segments obtained from the explanted hearts of transplant recipients were maintained at 37°C in culture medium containing 30% fetal bovine serum for fourteen days. Balloon angioplasty produced partial endothelial denudation and medial smooth muscle cell damage, both of which tended to be reversed after fourteen days in culture. Transverse histologic sections of cultured artery showed the development of a new intima containing smooth muscle cells identified by immunocytochemistry with anti-α-actin. Labeling of cultures with [³H] thymidine showed proliferating cells in the neointima. The data demonstrate that intimal proliferation occurs in organ culture of human coronary artery subjected to balloon angioplasty. They also suggest the possibility that the smooth muscle cells in the neointimal layer are the result of both migration and proliferation. This work was supported by grants from the National Heart Research Fund and the British Heart Foundation. Presented at the 34th Annual Congress, International College of Angiology, Budapest, Hungary, July 1992     

多沙唑嗪对血管狭窄和血清一氧化氮的影响

目的探讨多沙唑嗪对兔腹主动脉球囊损伤后血管狭窄的影响,及其与血清一氧化氮、血管内膜中膜平滑肌细胞增生的关系。方法23只新西兰兔随机分为正常对照组、球囊损伤组、多沙唑嗪组。正常对照组不予任何方式处理。另两组行腹主动脉球囊损伤术,同时多沙唑嗪组应用多沙唑嗪控释片4mg/d,观察各组血清一氧化氮以及血管损伤处血管狭窄、血管内膜中膜增殖细胞核抗原(PCNA)的变化。结果应用多沙唑嗪4周后多沙唑嗪组血清一氧化氮含量增高,血管损伤处血管内膜、外膜增生减轻,新生内膜面积减少,管腔面积增加,内弹力层和外弹力层包围面积增加,血管内膜中膜PCNA阳性平均灰度降低。结论多沙唑嗪可以抑制球囊损伤后兔腹主动脉血管的狭窄,抑制血管内膜中膜平滑肌细胞增殖,增加血清一氧化氮含量。     

缬沙坦对大鼠动脉损伤后细胞增殖的影响

目的探讨大鼠胸主动脉内膜剥脱后,内膜增生中缬沙坦对血管平滑肌细胞增殖及碱性成纤维细胞生长因子(bFGF)表达的影响,并探讨其内在机制。方法以大鼠胸主动脉内膜剥脱为实验模型,42只Wistar大鼠随机分为假手术组(n=6)、单纯损伤组与损伤+药物治疗组(简称药物治疗组)各18只。后两组大鼠行胸主动脉内膜剥脱术,药物治疗组术前6d至术后14d给予缬沙坦20mg.kg-1.d-1,余二组不给药。术后2、7、14d取材。应用免疫组化方法测定增殖细胞核抗原(PCNA)、bFGF在血管壁中的表达。结果单纯损伤组术后7、14d内膜面积持续增加,与假手术组有显著差异。药物治疗组术后14d的内膜面积与单纯损伤组相比有显著性差异。药物治疗组中PCNA、bFGF的表达均低于单纯损伤组。结论缬沙坦抑制PCNA及bFGF的表达,这可能是缬沙坦防治血管成形术后再狭窄的重要机制。     

Roscovitine抑制大鼠颈总动脉球囊损伤后内膜增生的研究

目的:观察roscovitine对球囊损伤后大鼠颈总动脉血管平滑肌细胞及内膜增生的抑制作用,以期提供新型的支架涂层药物。方法:建立大鼠颈总动脉球囊损伤模型模拟经皮冠状动脉腔内介入术(PCI)术后再狭窄,干预组损伤局部给予roscovitine(200μmol/L)孵育10分钟。14天后取材,免疫荧光染色观察roscovitine对局部血管平滑肌细胞增殖的作用;HE染色观察roscovitine对内膜增生的作用。结果:本研究建立了大鼠颈总动脉球囊损伤模型,球囊损伤后14天,局部血管平滑肌细胞增殖活跃、内膜增生明显。Roscovitine干预后,血管平滑肌细胞增殖率明显降低,内膜增生被显著抑制,管腔狭窄率和内膜中膜面积比值显著降低。结论:Roscovitine显著抑制大鼠颈总动脉球囊损伤后局部血管平滑肌细胞增殖,进而有效抑制内膜增生,降低再狭窄发生率。     

Elevated potassium intake inhibits neointimal proliferation in the swine coronary artery

Background:Previously, we reported that elevated extracellular potassium concentration in vitro inhibited proliferation and migration of vascular smooth muscle cells, formation of free radical compounds by macrophages, and reduced platelet sensitivity to agonists. More recently, we described a reduction in neointimal proliferation after balloon angioplasty injury in the carotid arteries of rats associated with an elevation of dietary potassium intake during a 4-week experiment. In the present study we conducted a similar investigation in the swine coronary artery balloon angioplasty model.Procedures:Two groups of seven castrated male swine were studied; for 28 days the normal potassium group consumed a diet containing 0.25% potassium and the high potassium group ate diet containing 2.0% potassium. After 14 days on the diet, balloon angioplasty was performed. After an additional 14 days on the same diets the hearts were removed, and normal and lesioned sections of the artery were analyzed histologically.Results:The neointimal area was markedly less in the high potassium group than in the normal potassium group, 0.33 ± 0.04 mm² v 0.74 ± 0.10 mm² (P < .004). Neointimal area-to-total wall area ratio in the normal potassium group averaged 0.199 ± 0.018, significantly greater than the ratio computed for the elevated potassium group, 0.120 ± 0.015 (P < .006).Conclusion:These results support the hypothesis that a high level of dietary potassium intake inhibits neointimal proliferation after balloon angioplasty in the swine coronary artery.     

全反式维甲酸对球囊损伤大鼠胸主动脉内皮后P16及增殖细胞核抗原表达的影响

为研究全反式维甲酸对球囊损伤大鼠胸主动脉内皮后内膜增生过程、P16及增殖细胞核抗原表达的影响，球囊剥脱大鼠胸主动脉内皮，并随机将大鼠分为手术组、全反式维甲酸治疗组及对照组，各组均于术前4天灌胃至实验结束，除对照组于术后14天处死大鼠外，全反式维甲酸治疗组和手术组分别在术后2天、7天、14天和28天处死大鼠并摘除大鼠胸主动脉，通过组织学检查和免疫组织化学技术检测术后14天和28天的内膜增生情况及术后2天、7天、14天和28天P16和增殖细胞核抗原的表达及全反式维甲酸(每天30mg／kg)灌胃对它们的影响。结果发现，对照组及内皮损伤后2天均无血管内膜增厚，7天内膜开始增生，28天血管平滑肌细胞增殖减弱，但细胞外基质增加。在手术组各时间点P16的表达变化不显著，增殖细胞核抗原于球囊损伤后2天在中膜明显表达，术后7天表达达到高峰，且主要在内膜表达，14天后逐渐下降。使用全反式维甲酸治疗后，内膜增生程度及增殖细胞核抗原的表达明显降低，而P16的表达在术后2天开始升高，14天达高峰。以上结果提示，全反式维甲酸可有效抑制血管内皮损伤后内膜的增生，其机制可能与促进P16表达和抑制增殖细胞核抗原表达，从而抑制血管平滑肌细胞的增殖有关。     

β_2-肾上腺素受体亚型激动对于血管平滑肌细胞增殖的影响

目的研究β2-肾上腺素受体亚型(beta2-adrenergic receptor,β2-AR)激动对于血管平滑肌细胞(VSMC)增殖的调控效应。方法应用携带重组β2-AR片段的腺病毒感染VSMC制备受体过表达模型。分别应用Zinterol(ZIN)以及异丙基肾上腺素(ISO)刺激生理状态和β2-AR过表达的平滑肌细胞后,采用四甲基偶氮唑盐(MTT)比色法和细胞计数法检测吸光度(A,曾称光密度OD)值和细胞数目的改变。结果ZIN刺激1天时A值开始下降(P<0.05),3天时抑制作用达高峰,抑制率为(32.00±1.62)%。细胞计数法测得ZIN激动3天时细胞数为对照组的(69.29±9.26)%。应用CGP20712A阻断β1-AR激活后,非选择性-βAR激动剂ISO刺激细胞后得到结果相似。特异性β2-AR拮抗剂ICI 118,551可逆转此抑制效应。ISO刺激过表达的β2-AR 3天时MTT检测结果相似。结论β2-AR亚型激动可抑制VSMC的增殖。