本文選題：慢性阻塞性肺疾病　切入點(diǎn)：氨茶堿　出處：《浙江大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 背景: 慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是常見的呼吸系統(tǒng)慢性疾病,是一種以呼吸道吸入有害氣體或有害顆粒致不完全可逆氣流受限為特征并呈進(jìn)行性發(fā)展的肺部非特異性炎癥性疾病,是世界慢性病防治重點(diǎn)之一。COPD是當(dāng)今危害人民健康主要疾病之一,發(fā)病率日益上升,由于病程遷延,且反復(fù)發(fā)作急性加重,嚴(yán)重影響了COPD患者的生活質(zhì)量,目前已成為各國(guó)醫(yī)療主要負(fù)擔(dān)之一。但是其具體發(fā)病機(jī)制仍不清楚,現(xiàn)在有包括氣道和肺部炎癥,蛋白酶/抗蛋白酶失衡,氧化/抗氧化失衡等學(xué)說。茶堿屬黃嘌呤類衍生物,為經(jīng)典的支氣管擴(kuò)張藥物,其作用主要是通過抑制腺苷酸磷酸二脂酶(PDE)而實(shí)現(xiàn),近年研究茶堿具有抑制炎癥反應(yīng)和免疫調(diào)節(jié)等作用。本實(shí)驗(yàn)采用煙熏及氣管內(nèi)滴入脂多糖建立COPD大鼠模型,并以氨茶堿大、小劑量對(duì)其干預(yù),觀察相關(guān)結(jié)果及分析有關(guān)機(jī)制。 研究目的: 本實(shí)驗(yàn)利用煙熏及氣管滴入脂多糖建立COPD大鼠模型。觀察COPD大鼠在肺功能、肺泡灌洗液、大鼠血白細(xì)胞計(jì)數(shù)與分類以及肺部組織的病理改變,同時(shí)觀察灌入氨茶堿大鼠在上述方面變化,研究氨茶堿在對(duì)COPD大鼠中的治療作用。 研究方法: 利用熏香煙及氣管滴入脂多糖法建立COPD大鼠模型(COPD組),二級(jí)雄性Sprague-Dawleg(SD)大鼠(清潔級(jí)),隨機(jī)分為對(duì)照組、模型組、氨茶堿小劑量組、氨茶堿大劑量組共四組,在不同時(shí)間點(diǎn)分批處死,進(jìn)行大鼠肺功能、肺泡灌洗液(BALF)、血中炎細(xì)胞計(jì)數(shù)和分類,并觀察肺組織的病理形態(tài)學(xué)改變。 結(jié)果: 1.動(dòng)物造模情況。實(shí)驗(yàn)動(dòng)物在實(shí)驗(yàn)過程中的表現(xiàn):模型組及各治療組大鼠早期出現(xiàn)躁動(dòng)不安并且先后出現(xiàn)咳嗽、氣急、精神萎靡、行動(dòng)遲緩、痰多納少、毛發(fā)枯黃等癥狀,之后出現(xiàn)體重減輕,進(jìn)食進(jìn)水量逐漸減少等表現(xiàn)。模型組大鼠肺體積略增大,正常對(duì)照組則始終未見上述表現(xiàn)。 2.COPD模型組氣道阻力明顯高于對(duì)照組,而其肺順應(yīng)性卻較對(duì)照組明顯下降;肺泡擴(kuò)大融合、肺泡數(shù)明顯減少;氣道阻力和肺順應(yīng)性之間有顯著的負(fù)相關(guān)性。 3.病理形態(tài)學(xué)觀察光鏡觀察健康對(duì)照組大鼠支氣管肺組織上皮結(jié)構(gòu)完整,支氣管纖毛排列整齊,肺泡結(jié)構(gòu)完整,在纖毛結(jié)構(gòu)間夾雜有少數(shù)杯狀細(xì)胞,管壁內(nèi)有少數(shù)散在的淋巴細(xì)胞。COPD模型組肺組織支氣管纖毛柱狀上皮細(xì)胞部分剝脫,纖毛粘連倒伏變性和壞死,有的纖毛明顯脫落,杯狀細(xì)胞增生,黏膜下層及肌層大量炎性細(xì)胞浸潤(rùn),可見支氣管平滑肌明顯增厚,管腔內(nèi)充滿大量中性粒細(xì)胞、肺泡巨噬細(xì)胞及黏液分泌物,肺泡擴(kuò)張融合,肺泡隔明顯增厚,其中可見炎細(xì)胞浸潤(rùn)和毛細(xì)血管擴(kuò)張充血。 4.COPD模型組BALF內(nèi)的白細(xì)胞總數(shù)、淋巴細(xì)胞數(shù)、中性粒細(xì)胞數(shù)均明顯較對(duì)照組增多,但巨噬細(xì)胞增多不明顯。中性粒細(xì)胞數(shù)量與白細(xì)胞總數(shù)呈顯著正相關(guān)(r=0.873,P＜0.01)中性粒細(xì)胞數(shù)量與淋巴細(xì)胞數(shù)量亦呈顯著的正相關(guān)性(r=0.712,P＜0.01)。 5.模型組大鼠與對(duì)照組大鼠血白細(xì)胞總數(shù)、巨噬細(xì)胞數(shù)、淋巴細(xì)胞數(shù)差別有顯著性意義見表3.3。結(jié)合表3.2發(fā)現(xiàn)BALF中性粒細(xì)胞數(shù)量與血中性粒細(xì)胞呈顯著正相關(guān)(r=0.675,P＜0.01)。 6.氨茶堿大、小劑量組均顯示了較好的改善COPD大鼠模型肺功能的作用:氣道阻力下降,肺順應(yīng)性提高;均有一定的抗炎作用,對(duì)氣道重塑形態(tài)學(xué)的改變亦有一定的改善作用:抑制了大鼠模型各級(jí)氣道管壁的厚度。 7.大劑量氨茶堿組較小劑量組對(duì)COPD大鼠的肺功能、抗炎作用、病理形態(tài)學(xué)的改善作用更明顯。 結(jié)論: 本實(shí)驗(yàn)所建立的COPD大鼠模型符合人類COPD的病理形態(tài)學(xué)特點(diǎn)。慢性氣道炎癥的反復(fù)刺激引起氣管黏膜下腺體增生肥大,淋巴細(xì)胞、漿細(xì)胞等炎癥細(xì)胞浸潤(rùn),支氣管纖毛柱狀上皮層增厚,皺褶高聳,杯狀細(xì)胞增生,支氣管腔內(nèi)中性粒細(xì)胞及黏液蓄積,平滑肌明顯增厚,黏膜下及外膜膠原纖維增生,終末呼吸細(xì)支氣管炎癥明顯,腔內(nèi)常有中性粒細(xì)胞聚集管壁纖維性增生增厚及平滑肌層增厚,即氣道重塑,最終導(dǎo)致氣流受限。氨茶堿對(duì)緩解COPD大鼠氣道壁增厚、減輕炎癥細(xì)胞浸潤(rùn),改善肺功能等起到重要作用。其中大劑量組在上述方面的作用更明顯。
[Abstract]:Background:
Chronic obstructive pulmonary disease (chronic obstructive pulmonary disease, COPD) is a common chronic respiratory diseases, is a kind of inhalation of harmful gases or particles caused by incompletely reversible airflow limitation is characterized by a progressive lung nonspecific inflammatory disease, is the world's chronic disease prevention and control is one of the key of.COPD the main diseases harm people's health, the incidence rate is rising, due to the prolonged course and recurrent episodes of acute exacerbation, seriously affecting the quality of life of patients with COPD, has become one of the main countries bear negative medical care. But its specific pathogenesis is still unclear, now include airway and lung inflammation, protease / antiprotease imbalance, etc. oxidant / antioxidant imbalance theory. Theophylline is a xanthine derivative, as a bronchodilator classic, its main function is through inhibition of adenylate phosphate Two lipase (PDE) has been achieved. In recent years, theophylline has inhibitory effects on inflammation and immune regulation. In this study, COPD rats were induced by smoking and intratracheal instillation of lipopolysaccharide, and the intervention was carried out with aminophylline at large or low doses, and the related results were observed and the mechanism was analyzed.
The purpose of the study is:
Smoked and intratracheal instillation of lipopolysaccharide in the rat model of COPD was constructed by using this experiment. COPD rats was observed in lung function, bronchoalveolar lavage fluid, the change of rat white blood cell count and classification of lung tissue pathology, and observe the changes of rats injected into aminophylline in the above aspects, the study of ammonia alkali in tea treatment effect on COPD in the rat.
Research methods:
The use of cigarette smoking and intratracheal instillation of lipopolysaccharide in the rat model of COPD was established (COPD group), two (SD) male Sprague-Dawleg rats (clean grade), were randomly divided into control group, model group, low-dose aminophylline group, aminophylline high-dose group four group, were killed in batches at different time point, lung the function of rat alveolar lavage fluid (BALF), inflammatory cell count and classification in the blood, and to observe the pathological changes in lung tissue.
Result:
1.. The animal model of experimental animal during the experiment showed: model group and treatment group rats appeared to be restless and has a cough, shortness of breath, listlessness, slow, sputum doner less, brown hair and other symptoms, after weight loss, decrease of food intake and inflow model. The lung volume of rats increased slightly, the normal control group has no such performance.
The airway resistance of 2.COPD model group was significantly higher than that of the control group, while the lung compliance was significantly lower than that of the control group. The alveolar enlargement and fusion and alveolar number decreased significantly, and there was a significant negative correlation between airway resistance and lung compliance.
3. pathological observation under light microscope, healthy control group lung tissue of rats with bronchial epithelial structural integrity, cilia arranged neatly, alveolar structure integrity, cilia structure with few goblet cell wall, there were a few scattered lymphocytes in.COPD model group lung tissue of bronchial ciliated columnar epithelial cells partially exfoliation, adhesion lodging degeneration and necrosis of cilia, some obvious cilia shedding, goblet cell hyperplasia, submucosa and muscular layer infiltration of inflammatory cells, visible bronchial smooth muscle thickening, the lumen filled with a large number of polymorphonuclear cells, alveolar macrophages and mucus secretion, alveolar expansion fusion, marked thickening of alveolar septa, which shows infiltration of inflammatory cells and telangiectasia congestion.
The total number of white blood cells in 4.COPD model group in BALF lymphocyte number, neutrophil counts were significantly increased compared with the control group, but the increase is not obvious. Macrophages were positively related to the total number of neutrophils and white blood cells (r=0.873, P < 0.01) number of neutrophils and the number of lymph cells also showed a significant positive correlation (r=0.712, P < 0.01).
5., there was a significant difference in the total number of white blood cells, macrophages and lymphocyte counts between the model group and the control group. According to table 3.3. combined with table 3.2, the number of BALF neutrophils was positively correlated with the blood neutrophils (r=0.675, P < 0.01).
6. a large group of small dose aminophylline, showed improvement in COPD rat model of pulmonary function better effect: decreased airway resistance, pulmonary compliance improved; anti-inflammatory effects of morphological changes on airway remodeling also have certain effect: the rat model of airway wall thickness at all levels decreased.
The small dose group of 7. large doses of aminophylline group had more obvious effect on the improvement of lung function, anti inflammatory and pathomorphology of COPD rats.
Conclusion:
The COPD rat model established in this experiment with the pathological features of human COPD. Repeated stimulation of chronic airway inflammation caused by tracheal submucosal gland hypertrophy, lymphocytes, plasma cells and other inflammatory cell infiltration, thickening of bronchial ciliated columnar epithelium, a tall, goblet cell hyperplasia, intraluminal neutrophils and mucus the accumulation of smooth muscle thickening, mucosa and adventitial collagen fiber hyperplasia, terminal respiratory bronchiolitis patients, cavity often neutrophil aggregation fibrous wall and hyperplasia of smooth muscle layer thickening, namely the airway remodeling, resulting in airflow limitation. Aminophylline to alleviate COPD rat airway wall thickening, inflammatory cell infiltration, improve play an important role in pulmonary function. The effect of high dose group in the above aspects of the more obvious.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R563.9;R-332

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 陳祥銀，趙青，趙磊，張蕙蓮，吳云清，斯勤，，原琪，周衛(wèi)輝，嚴(yán)儀昭;中藥制劑對(duì)煙霧刺激所致地鼠呼吸道炎癥的保護(hù)作用[J];基礎(chǔ)醫(yī)學(xué)與臨床;1999年01期

2 張旭晨,阮英茆,徐新林,褚燕,韓曉男,李亞輝;應(yīng)用彈性蛋白酶復(fù)制金黃地鼠肺氣腫模型[J];天津醫(yī)藥;1999年09期

3 曾勉,郭禹標(biāo),謝燦茂,嚴(yán)英碩,程?hào)|升,李志平,黃毓東,容中生;豬胰彈性蛋白酶肺氣腫模型復(fù)制的實(shí)驗(yàn)研究[J];現(xiàn)代康復(fù);2001年05期

4 遲春花,何冰,湯秀英,張紅;煙草霧吸入導(dǎo)致慢阻肺機(jī)制的實(shí)驗(yàn)研究——大鼠Clara細(xì)胞結(jié)構(gòu)及其分泌蛋白的變化[J];心肺血管病雜志;2000年03期

5 金焱,龐寶森,武維屏,馮淬靈,任傳云,牛淑潔,黃秀霞,崔巍,阮英茆;一種實(shí)驗(yàn)性大鼠慢性阻塞性肺疾病模型的建立[J];心肺血管病雜志;2004年03期

6 許建英,杜永成,趙鳴武,廖松林;大鼠慢性阻塞性肺疾病模型的建立[J];中國(guó)病理生理雜志;2000年04期

7 鄭鴻翱;建立慢性阻塞性肺疾病動(dòng)物模型方法的研究進(jìn)展[J];中國(guó)實(shí)驗(yàn)動(dòng)物學(xué)報(bào);2003年04期

8 馬楠,崔德健,梁延杰,佟欣,李玲,楊建發(fā);氣管內(nèi)注入脂多糖法建立大鼠慢性支氣管炎模型[J];中華結(jié)核和呼吸雜志;1999年06期

9 許滸,熊密,黃慶華,趙時(shí)宇,車東媛;細(xì)菌感染導(dǎo)致慢性阻塞性肺疾病大鼠模型的探討[J];中華結(jié)核和呼吸雜志;1999年12期

10 許三林,吳人亮,陳春蓮,郝春榮;上皮鈣粘附素在吸煙小鼠呼吸道上皮損傷修復(fù)中表達(dá)的研究[J];中華結(jié)核和呼吸雜志;1999年07期

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