本文選題：氣道狹窄 + 支架��； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：背景與目的:氣道狹窄是由氣道本身發(fā)生病變或者氣道外部病變的壓迫導(dǎo)致的氣管、支氣管的狹窄,其可引起反復(fù)發(fā)作的咳嗽、喘息、呼吸困難甚至窒息等,嚴重者可危及生命。氣道狹窄的處理較為困難,尤其是嚴重的氣道狹窄、多發(fā)性狹窄、一般情況較差的病人,手術(shù)治療效果有限。研究認為,無論是良惡性狹窄,氣道支架置入都取得了良好的治療效果[1,2]。但是,支架置入后部分患者會出現(xiàn)術(shù)后并發(fā)癥,如支架移位、支架斷裂、氣道再狹窄等,其中以氣道再狹窄的發(fā)生率最高。支架置入后,肉芽組織會通過支架網(wǎng)眼及支架兩端向支架內(nèi)生長,從而導(dǎo)致了氣道不同程度的再狹窄[3]。其在很大程度上阻礙了氣道支架的應(yīng)用。雷帕霉素靶蛋白信號傳遞通路在細胞增殖、凋亡和細胞周期的進程中發(fā)揮重要作用[4],因此阻斷mTOR信號傳遞通路可以抑制肉芽組織的增生。雷帕霉素通過抑制mTORC1阻斷mTOR信號傳遞通路。雷帕霉素藥物涂層支架已廣泛應(yīng)用于冠脈狹窄病人的介入治療,并取得了良好的臨床效果[5]。我們應(yīng)用雷帕霉素藥物涂層支架置入狹窄模型兔氣管中,觀察雷帕霉素對于肉芽組織增生的抑制作用,從而為氣道藥物涂層支架的臨床應(yīng)用提供實驗與理論依據(jù)。材料與方法:1.氣道狹窄動物模型的制備健康4月齡新西蘭大耳兔24只,肌內(nèi)注射麻醉后將實驗兔固定于實驗臺上,備皮、消毒、鋪巾,逐層切開皮膚、皮下組織、肌肉并暴露氣管,沿氣管軟骨環(huán)方向橫向切開約1cm,通過切口引入直徑6mm的尼龍毛刷,反復(fù)環(huán)形刮擦氣道黏膜,范圍約1-2cm。按上述方法將浸泡于無水酒精的毛刷再次刮擦氣道創(chuàng)面,直至肉眼觀察到毛刷表面出血。縫合氣管切口,并逐層縫合皮下肌肉及皮膚,消毒包扎。術(shù)后4周行MSCT觀察狹窄是否存在并測量狹窄程度。2.藥物涂層支架的制備將鎳鈦合金支架置入有機溶劑二氯甲烷中浸泡,后將支架置于超聲波清洗器中清洗去除支架表面雜質(zhì),置于烤箱中烤干備用。配制雷帕霉素與PLGA的浸涂液。將清洗過的鎳鈦合金支架置于浸涂液中充分浸泡,取出烘干備用。3.藥物涂層支架對于支架置入后預(yù)防氣道再狹窄的作用將18只實驗兔(氣道狹窄模型)分為裸支架對照組(n=6)和實驗組(n=12)。18只實驗兔均行肌肉注射麻醉,后在DSA下置入氣管支架(8mm*20mm)。對照組置入鎳鈦合金裸支架,實驗組置入雷帕霉素藥物涂層支架。分別于支架置入后1月、2月、3月處死實驗兔,處死前常規(guī)行MSCT檢測,測量各組氣管狹窄程度。解剖后取出氣管,對狹窄段氣管行病理學(xué)檢查。結(jié)果:1.氣管切開聯(lián)合黏膜損傷法建立氣管狹窄動物模型1只實驗兔于術(shù)中毛刷刮擦?xí)r出現(xiàn)嚴重氣道出血,死于窒息。1只實驗兔于術(shù)后第9天死亡,解剖可見氣管及支氣管內(nèi)大量黃白色膿性分泌物,胸腔內(nèi)可見大量胸腔積液,考慮死于肺部感染,余實驗兔一般情況良好,均存活至4周,其總體死亡率為8.3%,存活率為91.7%。MSCT掃描測量氣管總體狹窄程度為50.6%-82.8%,平均狹窄率為68.7%±9.4%。根據(jù)Myer-Cotton分度對狹窄率進行分級。其中45.5%(10/22)為Ⅱ度狹窄,54.5%為(12/22)為Ⅲ度狹窄。2.藥物涂層支架的制備通過浸涂法可成功制備雷帕霉素藥物涂層支架。應(yīng)用電子天平稱重提示涂層后支架重量較裸支架增大,電鏡掃描提示涂層藥物均勻覆蓋于支架表面。3.藥物涂層支架對于支架置入后抑制氣道再狹窄的作用支架置入后1月,實驗組與對照組均可見支架內(nèi)黃白色分泌物,支架上端較下端狹窄明顯,實驗組狹窄率小于對照組(62.3%±1.7%vs 81.6%±2.8%),二者差異有統(tǒng)計學(xué)意義(P0.05)。支架置入后2月,實驗組氣管狹窄程度較1月時明顯減小(47.4%±6.0%vs 62.3%±1.7%,P0.05)。支架置入后3月實驗組氣管狹窄程度與2月比無明顯差異(50.5%±3.8%vs 47.4%±6.0%,P0.05)。結(jié)論:雷帕霉素藥物涂層支架可抑制兔氣管損傷修復(fù)過程中肉芽組織的增生,從而降低支架置入后氣道再狹窄的發(fā)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
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R56

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