本文選題：油酸 + 急性肺損傷　； 參考：《第三軍醫(yī)大學》2013年碩士論文

【摘要】：背景：急性肺損傷(acute lung injury, ALI)是機體遭受多種病理刺激(如創(chuàng)傷、休克、嚴重感染、膿毒癥、缺氧等)后引起的肺微血管損害，以彌漫性肺泡毛細血管膜損傷導致肺水腫和肺不張為病理特征。近年來血管活性肽如尾加壓素Ⅱ(urotensinⅡ,UⅡ)及中介素(intermedin,IMD)對急性肺損傷(ALI)的影響開始受到國內外學者關注。尾加壓素Ⅱ是一種生長抑素樣環(huán)肽，屬于神經肽范圍，是迄今發(fā)現(xiàn)的最強的血管收縮肽，，具有收縮血管、改變血流動力學、調節(jié)內分泌以及促進細胞增殖等廣泛的生物學效應。中介素是一種新型肽類激素，屬降鈣素基因相關肽(calcitonin gene related peptide, CGRP)超家族成員，具有介導血管舒張，心肌收縮，調節(jié)細胞增殖、肥大、遷移、凋亡等多種生物學效應。�；撬�(Taurine, Tau)是人體組織細胞內含量最豐富的自由氨基酸，是體內重要的內源性抗損傷和細胞保護物質，具有廣泛的生理和藥理作用。 目的：研究牛磺酸對油酸所致急性肺損傷(ALI)大鼠的干預作用及其通過影響尾加壓素Ⅱ(UⅡ)及中介素(IMD)合成與分泌，探討其發(fā)揮肺保護作用的機制。 方法：采用制備油酸性急性肺損傷大鼠模型。實驗動物大鼠分為3組：對照組(C組)，油酸損傷組(A組)，牛磺酸治療組(T組)。分別于0h、6h、12h、24h四個時間點抽取動脈血2ml并取支氣管肺泡灌洗液(BALF)4ml，測定動脈血氧分壓(PaO2)，血漿及BALF中UⅡ、IMD濃度，測定肺濕干比(wet weight/dry weight W/D)進行統(tǒng)計學分析；肉眼觀察肺臟大體標本；普通光鏡及免疫組織化學檢查肺組織病理變化；電鏡觀察肺臟組織超微結構。 結果： 1.三組大鼠PaO2在0h、6h、12h均有顯著差異(P＜0.05)，6h、12h時T組高于A組。 2.三組肺組織W/D在0h、6h有差異(P＜0.05)，A組高于T組及C組(P＜0.05)。 3.三組血漿UⅡ在12h、24h時差異顯著(P＜0.05)，A組高于C組及T組(P＜0.05)；三組BALF UⅡ在0h、6h、12h差異顯著(P＜0.05)，A組高于T組及C組(P＜0.05)；A組血漿及BALF UⅡ在12h高于0h，6h及24h(P＜0.05)；T組血漿及BALF UⅡ在6h時最高(P＜0.05)。 4.三組血漿及BALF IMD在0h時比較有差異(P＜0.05)，A組高于T組及C組(P＜0.05)； A組血漿及BALF IMD在0h高于6h、12h、24h(P＜0.05)。 5.油酸致傷鼠肺肉眼見肺臟輕度腫脹，可見斑片狀出血壞死。光鏡觀察：A組肺泡萎陷，肺間質水腫，彌漫性出血，肺泡腔內可見大量紅細胞滲出和中性粒細胞浸潤，血漿蛋白滲出增多。T組肺組織滲出減輕，中性粒細胞及紅細胞滲出減少。 6.免疫組織化學染色結果顯示各組大鼠支氣管粘膜上皮細胞、平滑肌細胞，肺內血管內皮細胞、平滑肌細胞細胞膜及細胞質均有UⅡ與IMD陽性表達，A組與T組間表達無明顯差異。 7.電鏡觀察：A組肺泡腔內出血，毛細血管內皮細胞損傷，基底膜破壞，Ⅱ型肺泡上皮細胞部分板層小體排空，肺泡間質中膠原增多。T組損傷減輕，基底膜完整，未見明顯膠原纖維增生。 結論： 1.通過靜脈注射油酸可成功制備急性肺損傷大鼠動物模型。 2.UⅡ在油酸致急性肺損傷致病過程中，可能通過擴張血管，增加血管通透性，發(fā)揮促進損傷作用。IMD在油酸致急性肺損傷致病過程中早期升高，可能通過穩(wěn)定血管內皮細胞屏障功能、減輕血管滲出發(fā)揮其肺保護作用。 3.�；撬峥梢詼p輕油酸致大鼠急性肺損傷，其機制可能與促進UⅡ代謝降解，減輕毛細血管基底膜損傷后肺泡滲出有關，尚不能證明�；撬峥赏ㄟ^促進IMD合成與分泌減輕肺損傷。
[Abstract]:Background: acute lung injury (ALI) is the lung microvascular damage caused by various pathological stimuli (such as trauma, shock, severe infection, sepsis, anoxia, etc.), with diffuse alveolar capillary membrane injury leading to pulmonary edema and atelectasis. In recent years, vasoactive peptides such as caudal vasopressin II (urotensin The effect of U II) and Intermedin (IMD) on acute lung injury (ALI) has attracted the attention of scholars both at home and abroad. It is a somatostatin like peptide, which belongs to neuropeptide. It is the strongest vasoconstrictor found so far. It has contractile vessels, changes hemodynamics, regulates endocrine and promotes cell proliferation. Extensive biological effects. Mediator is a new peptide hormone, a member of the calcitonin gene related peptide (CGRP) superfamily, which mediates vasodilatation, myocardial contraction, regulation of cell proliferation, hypertrophy, migration, apoptosis and other biological effects. Taurine (Taurine, Tau) is the intracellular content of human tissue. The most abundant free amino acid is an important endogenous anti injury and cytoprotective substance in vivo. It has a wide range of physiological and pharmacological effects.
Objective: To study the effect of taurine on oleic acid induced acute lung injury (ALI) rats and to explore the mechanism of its protective effect on lung protection by affecting the synthesis and secretion of U II (U II) and mediator (IMD).
Methods: the rats were divided into 3 groups: the control group (group C), the oleic acid injury group (group A), the taurine group (group T). The arterial blood 2ml was extracted at the four time points of 0h, 6h, 12h and 24h, and the bronchial alveolar lavage fluid (BALF) 4ml, the arterial oxygen pressure (PaO2), the plasma and BALF, were measured. The concentration of IMD and the ratio of wet weight/dry weight W/D were statistically analyzed. The gross specimens of lung were observed by the naked eye, the pathological changes of lung tissue were examined by ordinary light microscopy and immunohistochemistry, and the ultrastructure of lung tissue was observed by electron microscope.
Result錛

本文編號：1929263