本文選題：動(dòng)物模型 + 放療��； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：背景和目的:氣道狹窄是臨床上常見的呼吸系統(tǒng)疾病,它是指由各種原因?qū)е碌臍夤芗?或)支氣管阻塞或外壓性狹窄,從而導(dǎo)致遠(yuǎn)端的阻塞性肺炎、阻塞性肺不張、或阻塞性肺氣腫,在臨床上常表現(xiàn)為胸悶、氣短等缺氧癥狀,嚴(yán)重狹窄可導(dǎo)致重度呼吸困難,加之痰液排出不暢甚至可導(dǎo)致窒息死亡,必要時(shí)需急診行氣管插管或氣管切開解除狹窄,改善癥狀。其按致病因素可分為良性氣道狹窄和惡性氣道狹窄,國內(nèi)導(dǎo)致良性氣道狹窄的病因大多數(shù)為氣管支氣管結(jié)核,其次是氣管插管或氣管切開等。氣道良性狹窄的治療既往多以外科手術(shù)切除為主,常見的手術(shù)方式有段性切除+端端吻合術(shù)、袖狀切除+氣道成形術(shù),術(shù)后吻合口狹窄發(fā)生率高,而且患者嚴(yán)重的氣道狹窄導(dǎo)致無法氣管插管,無法機(jī)械通氣,自然無法全麻進(jìn)行外科手術(shù)。近年來氣道內(nèi)支架置入快速解除氣道狹窄,緩解呼吸困難可取得立竿見影的效果,已得到廣大臨床醫(yī)生的認(rèn)可,隨著新型介入材料的研發(fā),介入技術(shù)越來越多的應(yīng)用于良性氣道狹窄疾病的治療,而且也逐漸替代外科手術(shù)成為氣道良性狹窄的首選,常見的介入手術(shù)治療包括:腔內(nèi)消融、球囊擴(kuò)張、內(nèi)支架置入等,然而氣道內(nèi)支架置入后的一些并發(fā)癥嚴(yán)重制約了其在良性氣道狹窄治療的推廣,其中最主要的是支架置入后氣道再狹窄,其病因多是由支架置入后肉芽組織過度增生所致,如何預(yù)防肉芽組織增生將對氣道再次狹窄的預(yù)防有深遠(yuǎn)意義。自從1895年倫琴發(fā)現(xiàn)X射線以來,放射治療在惡性腫瘤治療方面取得了很大發(fā)展,放療設(shè)備的不斷更新,使得放療亦常見用于良性病變的治療,如心血管支架置入后再狹窄的預(yù)防及皮膚瘢痕組織的治療,本實(shí)驗(yàn)通過建立兔良性氣道狹窄模型支架置入后X線外照射處理,比較不同劑量組下氣道的狹窄程度,探索X線外照射對兔氣道良性狹窄模型支架置入術(shù)后肉芽組織增生的抑制作用。材料和方法:1.氣道良性狹窄模型建立取健康的4月月齡新西蘭大耳兔32只,不限雌雄,重2.5~3kg,通過兔頸部氣管軟骨環(huán)間切開氣管,使用尼龍毛刷刮擦及無水酒精涂擦的方法制作氣管良性狹窄動(dòng)物模型,1個(gè)月后胸部CT掃描并氣道三維重建觀察氣道狹窄程度;2.X線透視下將8mm*20mm的鎳鈦合金裸支架置入于氣道良性狹窄模型的氣管狹窄處以解除狹窄,后隨機(jī)分為20Gy、30Gy、40Gy組及對照組,每組各8只實(shí)驗(yàn)兔,將20Gy組以7Gy/d劑量率照射2次,30Gy組以7Gy/d劑量率照射3次,40Gy組以8Gy/d劑量率照射3次,每次照射間隔5天,分別于4周及8周各處死各組一半實(shí)驗(yàn)動(dòng)物,處死前1天行胸部螺旋CT掃描,統(tǒng)計(jì)各組氣道狹窄率。實(shí)驗(yàn)結(jié)果:1.狹窄模型制作4周后所有動(dòng)物均存活,狹窄程度約42-85%,根據(jù)Myer—Cotton狹窄分級(狹窄面積減少程度,I度狹窄為0-50%,Ⅱ度狹窄為51-70%,Ⅲ度狹窄為71-99%,Ⅳ度狹窄為完全堵塞)評估,其中Ⅰ度狹窄(4/32),Ⅱ度狹窄(18/32),Ⅲ度狹窄(10/32)。2.外照射處理4周后,20Gy組氣道狹窄程度為(48.2±5.8)%;30Gy組氣道狹窄程度為(35.25±5.5)%;40Gy組氣道狹窄程度為(30.93±5.8)%;對照組氣道狹窄程度為(58.4±7.9)%;外照射后8周后,20Gy組氣道狹窄程度為(54.5±4.6)%;30Gy組氣道狹窄程度為(38.8±5.3)%;40Gy組氣道狹窄程度為(33.9±6.2)%;對照組氣道狹窄程度為(70.7±5.1)%。外照射后4周和8周發(fā)現(xiàn)對照組實(shí)驗(yàn)兔氣道平均狹窄程度與20Gy組、30Gy組、40Gy組平均氣道狹窄程度之間均有統(tǒng)計(jì)學(xué)意義(p0.05);20Gy組與30Gy組、20Gy組與40Gy組實(shí)驗(yàn)兔的氣道平均狹窄程度之間的差異則具有統(tǒng)計(jì)學(xué)意義(p0.05),30Gy組與40Gy組實(shí)驗(yàn)兔的氣道平均狹窄程度之間的差異無統(tǒng)計(jì)學(xué)意義(p0.05)。20Gy組相比于對照組可以減少肉芽組織增生,其實(shí)驗(yàn)組兔子所接受劑量較少,因此放射相關(guān)并發(fā)癥發(fā)生率較低,30Gy組相比于20Gy組在抑制肉芽組織增生方面有明顯差異,且相對并發(fā)癥較少,而40Gy組與30Gy組在抑制肉芽組織增生方面無明顯差異,放射相關(guān)并發(fā)癥較30Gy組嚴(yán)重,因此,推薦30Gy總劑量分次照射。3.病理及大體標(biāo)本觀察實(shí)驗(yàn)兔處死后,尸體解剖可見支架兩端可見明顯肉芽組織增生,表面可見白色膿性分泌物,氣道粘膜局部水腫。光鏡下可見氣管粘膜全層伴有大量纖維母細(xì)胞增生,肉芽纖維組織增生,局部軟骨可見炎細(xì)胞浸潤破壞。部分小血管管壁纖維素性壞死伴炎性細(xì)胞浸潤。黏膜下層及外層少量漿細(xì)胞為主的炎細(xì)胞浸潤。氣道管腔明顯狹窄,氣管黏膜全層可見少至中等量炎性細(xì)胞浸潤。結(jié)論:1、通過兔頸部氣管軟骨環(huán)間切開氣管,使用氣道尼龍毛刷刮擦及無水酒精涂擦成功制作良性氣管狹窄動(dòng)物模型,4周后氣道狹窄程度約(63.1±10.6)%;2、放療可以有效抑制兔良性氣道狹窄模型支架置入術(shù)后肉芽組織增生,本次實(shí)驗(yàn)推薦30Gy總劑量分次照射,對以后放射性氣道支架的研發(fā)提供基礎(chǔ)研究。
[Abstract]:Background and purpose: airway stenosis is a common clinical respiratory disease. It refers to trachea and (or) bronchial obstruction or external pressure stenosis caused by various causes, resulting in distal obstructive pneumonia, obstructive atelectasis, or obstructive emphysema, often characterized by hypoxic symptoms such as chest tightness, shortness of breath, and severe stenosis. The causes of severe respiratory distress, poor sputum discharge and even suffocation may lead to asphyxia. Emergency tracheal intubation or tracheotomy should be used to relieve the stenosis and improve the symptoms. The causes of the disease can be divided into benign airway stenosis and malignant airway stenosis. Endotracheal intubation or tracheotomy. The treatment of benign airway stenosis is mostly performed by surgical excision. The common surgical methods include segmental resection plus end to end anastomosis, sleeve resection plus airway plasty, high incidence of postoperative anastomotic stenosis, and severe airway stenosis leading to the failure of tracheal intubation, and no mechanical ventilation. Natural ventilation is not possible. In recent years, the internal airway stent implantation has been recognized by the vast number of clinicians. With the development of new interventional materials, more and more interventional techniques have been applied to the treatment of benign airway stenosis, and it is also gradually replaced by the new endotracheal stent. Surgery is the first choice for benign airway stenosis. Common interventional procedures include intracavitary ablation, balloon dilatation, and internal stent implantation. However, some complications after endobronchial stent implantation severely restrict the promotion of benign airway stenosis, most of which are airway restenosis after stent implantation, which are mostly caused by branches. How to prevent the proliferation of granulation tissue will be of profound significance for the prevention of re stenosis of the airway. Since the discovery of X ray in 1895, radiation therapy has made great progress in the treatment of malignant tumors, and the continuous renewal of radiotherapy equipment makes radiotherapy common for the treatment of benign lesions. Such as the prevention of restenosis after cardiovascular stent implantation and the treatment of skin scar tissue, the experiment was conducted to compare the stenosis degree of the lower airway in different dose groups by establishing the rabbit benign airway stenosis model after stent implantation, and to explore the inhibition of granulation tissue proliferation after external X-ray irradiation on rabbit airway benign stenosis model. Materials and methods: 1. healthy New Zealand rabbits were set up to establish healthy 4 month old New Zealand large ear rabbits, 32 of which were not limited to male and male, heavy 2.5~3kg. The trachea was cut through the tracheal cartilage ring in the neck of the rabbit. The animal model of benign tracheal stenosis was made by nylon brush scraping and anhydrous alcohol smear. The chest CT scan and airway three after 1 months. The degree of airway stenosis was observed by reconstruction. Under 2. X-ray fluoroscopy, 8mm*20mm NiTi bare metal stent was placed in the tracheal stenosis of the benign airway stenosis model, and then randomly divided into 20Gy, 30Gy, 40Gy and control groups, each group of 8 experimental rabbits, the 20Gy group was irradiated with 7Gy/d dose rate 2 times, the 30Gy group was irradiated with 7Gy/d dose rate 3 times, 40Gy group. At 8Gy/d dose rate 3 times, each time interval 5 days, 4 weeks and 8 weeks respectively, all the animals were killed in each group. The chest spiral CT scan was performed 1 days before death. The stenosis rate of each group was statistically analyzed. The results of the 1. stenosis model were all survived for 4 weeks, the stenosis was about 42-85%, according to the Myer Cotton stenosis classification (narrow area) The degree of reduction, the stenosis of I degree was 0-50%, the stenosis of degree II was 51-70%, the stricture of degree III was 71-99%, and the stenosis of degree IV was completely blocked. The stenosis of the airway was (48.2 + 5.8)% in 20Gy group and (35.25 + 5.5)% in 30Gy group after 4 weeks of stenosis (4/32), 18/32, and 10/32.2., and the airway stenosis in 30Gy group was (35.25 + 5.5)%; The degree of stenosis was (30.93 + 5.8)%, and the degree of airway stenosis in the control group was (58.4 + 7.9)%, and the degree of airway stenosis in group 20Gy was (54.5 + 4.6)% after 8 weeks of external irradiation, and the degree of airway stenosis in group 30Gy was (38.8 + 5.3)%, and the degree of airway stenosis in group 40Gy was (33.9 + 6.2)%, and the degree of airway stenosis in the control group was (70.7 + 5.1)%. The mean airway stenosis was statistically significant between the 20Gy group, the 30Gy group and the 40Gy group (P0.05). The difference between the 20Gy group and the 30Gy group, the 20Gy group and the 40Gy group was statistically significant (P0.05), and the difference between the average airway stenosis of the 30Gy group and the 40Gy group was the difference between the experimental rabbits and the 40Gy group. No statistical significance (P0.05) group.20Gy can reduce granulation tissue proliferation compared to the control group, the experimental group of rabbits received less dose, so the incidence of radiation related complications is lower, 30Gy group compared with the 20Gy group in the inhibition of granulation tissue proliferation is significantly different, and the relative complications are less, and the 40Gy group and the 30Gy group in the inhibition of meat. There was no significant difference in the proliferation of buds, and the radiation related complications were more serious than that in the 30Gy group. Therefore, the total dose of 30Gy was recommended for.3. pathological and gross specimens. After the death of the rabbit, the autopsy visible visible granulation tissue at both ends of the scaffold was visible, the white pus secretions were visible on the surface, and the local edema of the airway mucous membrane was visible. Under the light microscope, it was visible. The whole layer of trachea mucous membrane is accompanied by a large number of fibroblast proliferation, granulation tissue hyperplasia, local cartilage infiltration and infiltration of inflammatory cells. Some small vascular walls with cellulosic necrosis and inflammatory cells infiltrate. The submucosa and the outer layer of a small amount of plasma cells are mainly inflammatory cells. The airway lumen is obviously narrow and the whole layer of trachea mucous membrane can be seen less to the middle. Conclusion: 1, the animal model of benign tracheal stenosis was successfully made through tracheal incision between the tracheal cartilage ring of the rabbit's neck trachea and the tracheal nylon brush scraping and anhydrous alcohol smear. The degree of airway stenosis was about (63.1 + 10.6)% after 4 weeks. 2, radiotherapy could effectively inhibit the granulation tissue after stent implantation in rabbit benign airway stenosis model. The total dose fractionated irradiation of 30Gy is recommended in this experiment, which will provide basic research for the development of radioactive airway stent.

【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;R816.4

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本文編號：1848807