药物涂层支架对于支架置入后气道再狭窄作用的研究

发布时间：2018-05-24 13:40

本文选题：气道狭窄 + 支架　；参考：《郑州大学》2017年硕士论文

【摘要】：背景与目的:气道狭窄是由气道本身发生病变或者气道外部病变的压迫导致的气管、支气管的狭窄,其可引起反复发作的咳嗽、喘息、呼吸困难甚至窒息等,严重者可危及生命。气道狭窄的处理较为困难,尤其是严重的气道狭窄、多发性狭窄、一般情况较差的病人,手术治疗效果有限。研究认为,无论是良恶性狭窄,气道支架置入都取得了良好的治疗效果[1,2]。但是,支架置入后部分患者会出现术后并发症,如支架移位、支架断裂、气道再狭窄等,其中以气道再狭窄的发生率最高。支架置入后,肉芽组织会通过支架网眼及支架两端向支架内生长,从而导致了气道不同程度的再狭窄[3]。其在很大程度上阻碍了气道支架的应用。雷帕霉素靶蛋白信号传递通路在细胞增殖、凋亡和细胞周期的进程中发挥重要作用[4],因此阻断mTOR信号传递通路可以抑制肉芽组织的增生。雷帕霉素通过抑制mTORC1阻断mTOR信号传递通路。雷帕霉素药物涂层支架已广泛应用于冠脉狭窄病人的介入治疗,并取得了良好的临床效果[5]。我们应用雷帕霉素药物涂层支架置入狭窄模型兔气管中,观察雷帕霉素对于肉芽组织增生的抑制作用,从而为气道药物涂层支架的临床应用提供实验与理论依据。材料与方法:1.气道狭窄动物模型的制备健康4月龄新西兰大耳兔24只,肌内注射麻醉后将实验兔固定于实验台上,备皮、消毒、铺巾,逐层切开皮肤、皮下组织、肌肉并暴露气管,沿气管软骨环方向横向切开约1cm,通过切口引入直径6mm的尼龙毛刷,反复环形刮擦气道黏膜,范围约1-2cm。按上述方法将浸泡于无水酒精的毛刷再次刮擦气道创面,直至肉眼观察到毛刷表面出血。缝合气管切口,并逐层缝合皮下肌肉及皮肤,消毒包扎。术后4周行MSCT观察狭窄是否存在并测量狭窄程度。2.药物涂层支架的制备将镍钛合金支架置入有机溶剂二氯甲烷中浸泡,后将支架置于超声波清洗器中清洗去除支架表面杂质,置于烤箱中烤干备用。配制雷帕霉素与PLGA的浸涂液。将清洗过的镍钛合金支架置于浸涂液中充分浸泡,取出烘干备用。3.药物涂层支架对于支架置入后预防气道再狭窄的作用将18只实验兔(气道狭窄模型)分为裸支架对照组(n=6)和实验组(n=12)。18只实验兔均行肌肉注射麻醉,后在DSA下置入气管支架(8mm*20mm)。对照组置入镍钛合金裸支架,实验组置入雷帕霉素药物涂层支架。分别于支架置入后1月、2月、3月处死实验兔,处死前常规行MSCT检测,测量各组气管狭窄程度。解剖后取出气管,对狭窄段气管行病理学检查。结果:1.气管切开联合黏膜损伤法建立气管狭窄动物模型1只实验兔于术中毛刷刮擦时出现严重气道出血,死于窒息。1只实验兔于术后第9天死亡,解剖可见气管及支气管内大量黄白色脓性分泌物,胸腔内可见大量胸腔积液,考虑死于肺部感染,余实验兔一般情况良好,均存活至4周,其总体死亡率为8.3%,存活率为91.7%。MSCT扫描测量气管总体狭窄程度为50.6%-82.8%,平均狭窄率为68.7%±9.4%。根据Myer-Cotton分度对狭窄率进行分级。其中45.5%(10/22)为Ⅱ度狭窄,54.5%为(12/22)为Ⅲ度狭窄。2.药物涂层支架的制备通过浸涂法可成功制备雷帕霉素药物涂层支架。应用电子天平称重提示涂层后支架重量较裸支架增大,电镜扫描提示涂层药物均匀覆盖于支架表面。3.药物涂层支架对于支架置入后抑制气道再狭窄的作用支架置入后1月,实验组与对照组均可见支架内黄白色分泌物,支架上端较下端狭窄明显,实验组狭窄率小于对照组(62.3%±1.7%vs 81.6%±2.8%),二者差异有统计学意义(P0.05)。支架置入后2月,实验组气管狭窄程度较1月时明显减小(47.4%±6.0%vs 62.3%±1.7%,P0.05)。支架置入后3月实验组气管狭窄程度与2月比无明显差异(50.5%±3.8%vs 47.4%±6.0%,P0.05)。结论:雷帕霉素药物涂层支架可抑制兔气管损伤修复过程中肉芽组织的增生,从而降低支架置入后气道再狭窄的发生率
[Abstract]:Background and purpose: airway stenosis is the trachea caused by the lesion of the airway itself or the oppression of the external airway, the stenosis of the bronchus, which can cause recurrent coughs, wheezing, dyspnea and even asphyxia. The serious person can endanger life. The treatment of airway stenosis is more difficult, especially severe airway stenosis and multiple narrowing. Narrow, generally poor patients have limited surgical treatment. The study believes that both benign and malignant stenosis, airway stent placement has achieved good therapeutic effect [1,2]., but after stent placement, postoperative complications, such as stent displacement, stent fracture, airway restenosis, and so on, are most likely to occur in the airway restenosis. After the stent implantation, the granulation tissue grows through the stents and the scaffolds at both ends, resulting in a different degree of restenosis of the airway [3]. which greatly hinders the application of the airway stents. The rapamycin target protein signaling pathway plays an important role in the process of cell proliferation, apoptosis and cell cycle, [4], Therefore, blocking the mTOR signaling pathway can inhibit the proliferation of granulation tissue. Rapamycin can block the mTOR signaling pathway by inhibiting mTORC1. The rapamycin drug coated stent has been widely used in the interventional treatment of patients with coronary stenosis, and good clinical effect has been achieved. [5]. we used the rapamycin drug coating stent to be placed in the narrow area. In the narrow model rabbit trachea, the inhibitory effect of rapamycin on the proliferation of granulation tissue was observed, thus providing experimental and theoretical basis for the clinical application of the airway drug coating scaffold. Materials and methods: 24 healthy New Zealand rabbits were prepared by the 1. airway stenosis model. The experimental rabbits were fixed on the experimental platform after intramuscular injection of anesthesia. Skin preparation, disinfection, scarf, skin incision by layer by layer, subcutaneous tissue, muscle and exposure to trachea, lateral incision of 1cm along the direction of tracheal cartilage ring, nylon brush with diameter 6mm through incision, repeated circular scraping of the airway mucosa, about 1-2cm. in the above method to scrape the wound of the airway again by soaking in the unhydrated alcohol brush until the naked eye is observed. Bleeding on the surface of brush, suture the incision of the trachea, suture the subcutaneous muscles and skin by layer by layer, and sterilize it. 4 weeks after the operation, MSCT observation was performed to observe the existence of the stenosis and the measurement of the stenosis degree of the.2. drug coated stent. The nickel titanium alloy stent was soaked in the organic solvent dichloromethane, and then the stent was cleaned and removed in the ultrasonic cleaner. The effect of 18 experimental rabbits (airway stenosis model) was divided into bare stent control group (n). The effect of 18 rabbits (airway stenosis model) was divided into the bare stent control group (n). =6) and the experimental group (n=12).18, only the experimental rabbits were injected with the intramuscular anesthesia, then the trachea stent (8mm*20mm) was placed under the DSA. The control group was implanted with NiTi alloy bare scaffold, and the experimental group was placed with the rapamycin drug coating stent. The experimental rabbits were sacrificed in January, February and March respectively. The routine MSCT test was performed before death, and the degree of tracheal stenosis was measured in each group. Results: 1. tracheotomy combined with mucosal injury was used to establish an animal model of trachea stenosis in 1 rabbits. Severe airway bleeding occurred during the brush scraping during the operation, and the.1 rabbits died of asphyxia at ninth days after the operation. A large number of yellowish white pyogenic scores in the trachea and bronchus were found. A large amount of pleural effusion was found in the thoracic cavity, and the rabbits were considered to die from pulmonary infection. The rabbits survived a good general condition and survived to 4 weeks. The total mortality rate was 8.3%. The survival rate was 50.6%-82.8% with 91.7%.MSCT scan, and the average stenosis rate was 68.7%. 9.4%. The stenosis rate was graded according to the Myer-Cotton degree. 45 .5% (10/22) is 2 degree narrow and 54.5% (12/22) is (12/22) 3 degree narrow.2. drug-eluting stent, the preparation of rapamycin drug coating stent can be successfully prepared by dip coating method. The weight of the stent is larger than that of the bare scaffold. The electron microscope scan suggests that the coated drugs cover the.3. drug coating scaffold on the surface of the stent. The effect of stent implantation to inhibit airway restenosis was observed in the experimental group and the control group in January. The experimental group and the control group showed the yellow and white secretions in the stent. The upper end of the stent was narrower than the lower end. The stenosis rate of the experimental group was less than that of the control group (62.3% 1.7%vs 81.6% + 2.8%), and the difference of the two was statistically significant (P0.05). After the stent implantation, the experimental group was narrowed in the trachea after the stent implantation. The narrower degree was significantly lower than that in January (47.4% + 6.0%vs 62.3% + 1.7%, P0.05). The degree of tracheal stenosis in the experimental group was not significantly different from that in February (50.5% + 3.8%vs 47.4% + 6%, P0.05). Conclusion: rapamycin drug coated stent could inhibit the proliferation of granulation tissue during the repair of trachea injury in rabbits, thus reducing the gas after stent implantation. Incidence of restenosis of the tract
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R56

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