低能量约激光局部照射预防血管成形术后再狭窄的实验研究

目的 评价低能量红激光局部照射以血管成形术后再狭窄的预防作用。方法 对雄性新西兰白兔进行腹主动脉和髂动脉球囊拉伤（单纯拉伤组５０只）和拉伤后低能量密度的红激光局部照射（激光照射组５０只）。两组分别于术后３天、１周、２周、４周和８周分批进行血和病理形态学、氚标记胸腺嘧啶核苷（＾３Ｈ－ＴＤＲ）掺透实验和血管造影检查。结果 血管拉伤后８周造影显示，激光照射组血管最小内径显大于单纯拉伤组（Ｐ〈０．０５）     

低强度红激光局部照射影响血管损伤后重塑的实验研究

目的评价低能量红激光局部照射（ＬＰＲＬＩ）对血管损伤后重塑模式的影响。方法雄性新西兰白兔１００只,随机分为球囊拉伤组和球囊拉伤加激光照射组。球囊拉伤右髂动脉后,应用激光球囊照射拉伤局部,总的能量密度为０．９Ｊ／ｃｍ＾２。分别于术后３天、１周、２周、４周和８周分批处死动物,原位固定后截取病变血管进行病理组织学和免疫组织化学检测。最后１批动物在取材前进行髂动脉造影。结果拉伤后３天单纯拉伤组管腔横截面积     

低强度红激光局部照射抑制血管成形术后血管重塑的？…

目的观察低强度红激光照射（Ｌｏｗ Ｐｏｗｅｒ Ｒｅｄ Ｌａｓｅｒ Ｉｒｒａｄｉａｔｉｏｎ，ＬＰＲＬＩ）后局部血管组织Ⅰ型胶原（Ｃｏｌ Ⅰ）ｍＲＮＡ、细胞间黏附分子－１（ＩＣＡＭ－１）的表达和血管平滑肌细胞（ＶＳＭＣ）凋亡，探讨ＬＰＲＬＩ抑制动脉粥样硬化兔血管成形术后收缩性血管重塑的可能机制。方法建立动脉粥样硬化兔的血管损伤模型。１００只新西兰白兔随机分为单纯血管拉伤组和单纯拉伤＋激光照射组。对术后     

低强度红激光局部照射对血管成形术后血管内皮功能的影响

目的　观察低强度红激光照射 (LPRLI)对动脉粥样硬化兔血管成形术后血管内皮修复和功能的影响。方法　新西兰白兔 40只 ,随机分为单纯球囊拉伤组和球囊拉伤并激光照射组各 2 0只 ,建立动脉粥样硬化兔血管损伤模型。激光照射组于球囊拉伤后应用激光球囊导管对损伤血管进行局部照射。对术后第 4周的两组动物 ,固定部位剪取拉伤组和激光照射组损伤的腹主动脉血管 ,采用离体血管功能实验方法 ,观察兔腹主动脉环的张力变化和损伤血管内皮细胞的修复情况。结果　经过LPRLI的兔损伤腹主动脉的内皮依赖性舒张功能明显强于单纯拉伤组血管。右髂动脉损伤段血管损伤面积 ,单纯拉伤组 (6 1 11± 7 12 )mm2 ,激光照射组 (96 71± 8 2 0 )mm2 ,后者的修复面积明显大于前者(P <0 0 1)。结论　LPRLI对动脉粥样硬化兔损伤动脉的内皮依赖性舒张功能具有保护作用并可以促进损伤血管内皮修复     

血脂康对我血管成形术 内膜增殖及C—nyc基因表达的影响

目的 探讨血脂康对家免血管成形术后血管内膜增殖及Ｃ－ｍｙｃ基因表达的影响。方法 ３０只高胆固醇喂养４周的日本雄性大白兔,用球囊导管剥脱腹主动脉内皮４周后,对局部动脉粥样硬化狭窄部行球囊成形术后随机分为对照组、高脂组和血脂康组。４周后采集局部血管行病理形态、反转录ＰＣＲ法Ｃ－ｍｙｃ基因半定量及其Ｃ－ｍｙｃ蛋白免疫组化分析。结果 病理形态学观察血脂康组血管内膜面积小于对照组（Ｐ〈０．０５）,对照组血管     

不同化疗方案治疗老年人急性髓系白血病疗效观察

４５例老年人急性髓系白血病经不同化疗方案治疗，ＨＡ方案剂量个体化组治疗１９例，完全缓解（ＣＲ）率５２６％；ＤＡ方案组治疗８例，ＣＲ率５０％；ＨＯＡＰ方案组治疗９例，ＣＲ率４４４％；小剂量阿糖胞苷（ＬＤＡｒａＣ）组治疗９例，ＣＲ率１１１％。ＨＡ方案剂量个体化组ＣＲ率显著高于ＬＤＡｒａＣ组（Ｐ＜００５）。骨髓抑制的发生率和治疗相关病死率分别为３６８％和５６％（ＨＡ）、７５％和３７５％（ＤＡ）、４４４％和２２２％（ＨＯＡＰ）、３３３％和１１１％（ＬＤＡｒａＣ），ＤＡ方案组治疗相关病死率显著高于ＨＡ方案剂量个体化组（Ｐ＜００２５）。联合化疗治疗３６例，ＣＲ率为５０％，高于单用ＬＤＡｒａＣ组（Ｐ＜００５），骨髓抑制发生率为４７２％（１７／３６），治疗相关病死率为１６７％（６／３６），同ＬＤＡｒａＣ组比较无显著性（Ｐ＞００５）。     

乙型肝炎及原发性肝癌患者sIL-2R的变化

目的探讨ｓＩＬ２Ｒ水平与乙型肝炎病情的关系及其在原发性肝癌早期诊断中的价值．方法以ＥＬＩＳＡ法动态检测１１３例乙型肝炎及６例原发性肝癌患者ｓＩＬ２Ｒ水平，另选３１例健康体检者作对照组．结果以ｑ检验、ｔ检验进行统计学处理（微机处理，ＰＯＭＳ２００版）．结果各型乙型肝炎ｓＩＬ２Ｒ水平均显著高于正常对照（ＮＣ）组（Ｐ＜００１），其顺序依次为：ＨＣＣ＞ＣＳＨ＞ＣＨ（ＩＩ）＞ＬＣ＞ＣＨ（ＩＩ）＞ＡＨ＞ＣＨ（Ｉ）＞ＮＣ．ＨＣＣ组ｓＩＬ２Ｒ均值达正常值的２倍以上，且与ＣＨ（Ｉ），ＣＨ（Ｉ），ＡＨ间存在显著性差异（Ｐ＜００１，＜００５及＜００５）；ＣＨ（ＩＩ）组显著高于ＣＨ（Ｉ）组（Ｐ＜００１）．ＨＢｅＡｇ阳性组及ＨＢＶＤＮＡ阳性组ｓＩＬ２Ｒ水平显著高于阴性组．结论ｓＩＬ２Ｒ是监测乙型肝炎病情、ＨＢＶ复制及诊断早期原发性肝癌的一项敏感标志．     

103Pd同位素支架预防支架内再狭窄的实验研究

目的 探讨103Pd同位素支架对支架植入术后再狭窄的预防作用,方法 对雄性新西兰白兔50只进行腹主动脉球囊拉伤后,分别置入103pd同位素支架（同位素支架组）和普通支架（普通支架组）各25只。两组分别于术后3d和1,2,4,8周分批进行血管病理形态学,免疫组织化学测定和血管造影检查。结果 血管拉伤后8周,血管造影显示,同位素支架组血管最小内径显大于普通支架组（P＜0．05）,血管狭窄程度明显减低（P＜0．05）,病理形态学和免疫化学染色分析表明,两组血管损伤程度相同,受同位素辐射作用后,血管内膜增生到显抑制,管腔狭窄程度减轻,结论 103Pd同位素支架在动物实验中具有明显预防支架内血管再狭窄的作用。     

血脂康对高脂饮食家兔血管内皮细胞功能的保护作用

目的探讨血脂康对高胆固醇饮食家兔血管内皮细胞功能的保护作用。方法健康纯种新西兰白兔３０只，随机分层分组法分为对照组（普通饲料），高脂组（普通饲料＋１５％胆固醇），治疗组（普通饲料＋１５％胆固醇＋血脂康０８ｇ·ｋｇ－１·ｄ－１），在实验不同阶段，观察各组家兔血清脂质、一氧化氮及血浆内皮素、前列环素、血栓素含量及血管内皮细胞病理形态学改变。结果实验前各组血清总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、低密度脂蛋白胆固醇（ＬＤＬＣ）、血浆内皮素（ＥＴ）１、血清一氧化氮（ＮＯ）、血浆血栓素（ＴＸ）Ｂ２及６酮前列腺素（ＰＧ）Ｆ１α等无明显差异。实验１２周，高脂组、血脂康治疗组血清ＴＣ、ＴＧ、ＬＤＬＣ及血浆ＥＴ１、ＴＸＢ２及ＴＸＢ２／６酮ＰＧＦ１α比值明显高于对照组，但治疗组明显低于高脂组（Ｐ值均＜０．０５）；血浆ＮＯ低于对照组（Ｐ＜０．０５），但治疗组高于高脂组（Ｐ＜０．０５）。病理结果显示：血脂康治疗组主动脉、冠状动脉粥样硬化病变及血管内皮细胞损伤明显轻于高脂组。结论血脂康具有明显的调整脂质代谢及保护血管内皮细胞功能的作用。     

老年吸烟者肺癌H-ras基因突变的研究

目的探讨老年吸烟者肺癌Ｈｒａｓ基因变化的意义。方法对３３例吸烟肺癌和２２例不吸烟肺癌患者采用纤维支气管镜毛刷刷取支气管脱落细胞,应用ＰＣＲＲＦＬＰ方法进行Ｈｒａｓ基因突变检测。结果肺癌中Ｈｒａｓ基因总突变率为５２７％（２９／５５）,其中吸烟组肺癌Ｈｒａｓ基因突变率为６６７％,不吸烟组肺癌为３１８％,二者差异有显著性（Ｐ＜００５）,吸烟组肺鳞癌患者Ｈｒａｓ基因突变率为７００％,明显高于不吸烟组肺鳞癌患者的１６７％（Ｐ＜００５）。结论提示Ｈｒａｓ基因可能是被烟草激活的一个特殊位点,吸烟是导致Ｈｒａｓ基因突变的重要因素。     

Photoremodeling of Arterial Wall Reduces Restenosis After Balloon Angioplasty in an Atherosclerotic Rabbit Model

Objectives. This study evaluated the long-term impact of endoluminal low power red laser light (LPRLL) on restenosis in an atherosclerotic rabbit model.Background. Despite widespread application of balloon angioplasty for treatment of coronary artery disease, restenosis limits its clinical benefits. Restenosis is a complex process and may be partly attributed to the inability of the vascular endothelium to regenerate and cover the denuded area at the site of arterial injury. We previously demonstrated that LPRLL stimulates endothelial cell proliferation in vitro and contributes to rapid endothelial regeneration after balloon injury in nonatherosclerotic rabbits.Methods. Rabbit abdominal aortas (n = 12) were treated in separate zones with balloon dilation and balloon dilation plus laser illumination. Endoluminal laser therapy was performed using a laser-balloon catheter delivering a single dose of 10 mW for 3 min from a helium-neon laser (632 nm). Angiography was performed before and after treatment and was repeated 8 weeks before harvesting the aortas.Results. Quantitative angiographic analysis demonstrated no differences in the minimal lumen diameter (MLD) between the two zones before treatment; an increase in the MLD in both zones after balloon angioplasty and a significant versus slight reduction of the MLD in the balloon treatment versus balloon plus laser zones at 8 weeks. Histologic examination showed a very high level of myointimal hyperplasia in the balloon treatment zones but a minimal level in the LPRLL-treated zones. Morphometric analysis revealed a statistically significant difference in the lumen area, intimal area and intima/media ratio between the balloon versus balloon plus laser treatment sites.Conclusions. Our experimental data indicate that endoluminal irradiation with LPRLL prevents restenosis after balloon angioplasty in an atherosclerotic rabbit model.     

~(103)Pd同位素支架预防支架内再狭窄的实验研究

目的　探讨10 3 Pd同位素支架对支架植入术后再狭窄的预防作用。方法　对雄性新西兰白兔 5 0只进行腹主动脉球囊拉伤后 ,分别置入10 3 Pd同位素支架 (同位素支架组 )和普通支架 (普通支架组 )各 2 5只。两组分别于术后 3d和 1、2、4、8周分批进行血管病理形态学、免疫组织化学测定和血管造影检查。结果　血管拉伤后 8周 ,血管造影显示 ,同位素支架组血管最小内径显著大于普通支架组 (P <0 .0 5 ) ;血管狭窄程度明显减低 (P <0 .0 5 ) ;病理形态学和免疫化学染色分析表明 ,两组血管损伤程度相同。受同位素辐射作用后 ,血管内膜增生受到显著抑制 ,管腔狭窄程度减轻。结论10 3 　Pd同位素支架在动物实验中具有明显预防支架内血管再狭窄的作用。     

重组水蛭素对兔髂总动脉球囊损伤后内膜增殖影响的实验研究

目的 :探讨重组水蛭素对兔髂总动脉球囊损伤后内膜增殖的影响。方法 :2 4只纯种日本大耳白兔随机分成肝素对照组 （n=12 ）和重组水蛭素组 （n=12 ） ,采用兔髂总动脉球囊扩张损伤后内膜增殖动物模型 ,术后 2周和 4周复查血管造影 ,术后 4周处死动物取髂总动脉标本。结果 :用药组术后 2周和 4周平均髂总动脉直径均较对照组明显增加 （P<0 .0 1） ,4周后新生内膜面积显著减少 （P<0 .0 1） ,管腔面积明显扩大 （P<0 .0 1）。结论 :重组水蛭素可显著减轻兔髂总动脉球囊扩张损伤后新生内膜增殖和管腔的狭窄     

192Ir血管内照射防止兔球囊血管成形术后再狭窄

目的　旨在检验1 92 Ir血管内照射对兔球囊血管成形术后再狭窄的作用。方法　建立兔髂动脉粥样硬化模型 ,对病变血管行球囊成形术 ,同时随机分为对照组、10Gy照射组和 18Gy照射组。以导管导入1 92 Ir放射性导丝对照射组动物的扩张处进行血管内照射。 4周后处死动物 ,取出血管标本 ,进行病理组织学分析。结果　 18Gy照射组最终管腔面积较对照组及 10Gy照射组大 (P <0 0 5 ) ,18Gy照射组内膜面积较小 (P <0 0 5 )。结论　提示1 92 Ir血管内照射可防止球囊血管成形术后再狭窄 ,其效果与照射剂量相关 ,其机制涉及抑制新生内膜增殖。     

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

BACKGROUND. Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of clinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. METHODS AND RESULTS. Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief approximately 30 degrees C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 microns to 330 microns (r = 0.94). CONCLUSIONS. Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation.     

Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.     

Intra-arterial stenting in the atherosclerotic rabbit

The major problem associated with percutaneous transluminal coronary angioplasty is recurrence of the stenotic lesion. Balloon catheter-mounted intracoronary stent devices may reduce restenosis by improving luminal morphology and flow characteristics. This study assessed the effects of a stainless steel wire, interdigitating coil stent on restenosis in the atherosclerotic rabbit model. Fifteen cholesterol-fed rabbits with preexisting iliac arterial lesions induced by balloon deendothelialization were instrumented in one iliac artery with a 2.0-mm diameter stent after balloon dilatation; the contralateral iliac lesion was treated by dilatation only to serve as a control. The animals were given heparin with aspirin (60 mg) and aspirin every 3rd day until death. Arteriography was repeated 4 weeks after stenting, just before death. Tissue sections from stented and control arterial segments were analyzed morphometrically. Stented arteries had a significantly larger luminal diameter at restudy, whether measured by arteriography (1.38 +/- 0.19 vs. 0.94 +/- 0.35 mm, p less than 0.01) or from tissue sections (1.26 +/- 0.18 vs. 0.81 +/- 0.30 mm, p = 0.0001). Wall thickness of the stented segment was slightly, but significantly, less than the control segment (436 +/- 143 vs. 532 +/- 221 microns, p less than 0.05). Scanning electron microscopy of five stented atherosclerotic rabbit aortas revealed regeneration of a nonthrombogenic, confluent, flow-directed endothelium by 4 weeks after placement. Intra-arterial stenting may be of benefit in the prevention of restenosis by the preservation of a larger functional lumen and by a decrease in the neointimal hyperplastic response to arterial injury.     

Photodynamic therapy for the prevention of intimal hyperplasia in balloon-injured rabbit arteries

This study was performed to demonstrate accumulation of the photosensitizer hematoporphyrin derivative (HPD) in atherosclerosis and to determine whether intimal hyperplasia, the main cause of restenosis after angioplasty, can be inhibited by photodynamic therapy (PDT). Forty Japanese White rabbits were subjected to balloon endothelial injury in the common iliac artery. Five groups of rabbits, ie, immediately after, or 3, 7, 14 or 28 days after the balloon injury, were injected with HPD. These rabbits were sacrificed 24h after HPD administration, and HPD fluorescence was investigated in the injured arteries by fluorescence microscopy. Other groups of rabbits were injected with HPD 24h before PDT, and they were then subjected to intravascular Hg-Xe flash-lamp irradiation immediately after (0D-PDT), or 3 days (3D-PDT), 7 days (7D-PDT), or 14 days (14D-PDT) after the balloon injury. All rabbits were sacrificed 28 days after the balloon injury, and histological sections of PDT-treated arteries were examined by light microscopy. Slight, uniform HPD accumulation was observed in the injured media immediately after the balloon injury, and throughout the entire media and the neointima on day 7. On day 14, HPD accumulation had diminished in the media and increased in the intima, and on day 28 no HPD remained in the media. In the 0D- or 3D-PDT groups, no inhibition of intimal hyperplasia was observed. In contrast, there was significant inhibition of intimal hyperplasia in the 7D- and 14D-PDT groups, and the most effective inhibition was in the 7D-PDT group. This study demonstrated that PDT with HPD inhibits smooth muscle cell growth and decreases the intimal hyperplasia response in rabbits.     

Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid

OBJECTIVE: Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitizing drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury. METHODS: Studies were undertaken on 13 juvenile Large White-Landrace crossbred pigs (15-20 kg). After intravenous administration of the photosensitizing agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by over-distension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry. RESULTS: Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P = 0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P = 0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P = 0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels. CONCLUSIONS: Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures.