牛磺酸对油酸致急性肺损伤大鼠尾加压素Ⅱ与中介素的影响及其肺保护作用

发布时间：2018-05-24 13:43

  本文选题：油酸 + 急性肺损伤　； 参考：《第三军医大学》2013年硕士论文

【摘要】：背景：急性肺损伤(acute lung injury, ALI)是机体遭受多种病理刺激(如创伤、休克、严重感染、脓毒症、缺氧等)后引起的肺微血管损害，以弥漫性肺泡毛细血管膜损伤导致肺水肿和肺不张为病理特征。近年来血管活性肽如尾加压素Ⅱ(urotensinⅡ,UⅡ)及中介素(intermedin,IMD)对急性肺损伤(ALI)的影响开始受到国内外学者关注。尾加压素Ⅱ是一种生长抑素样环肽，属于神经肽范围，是迄今发现的最强的血管收缩肽，，具有收缩血管、改变血流动力学、调节内分泌以及促进细胞增殖等广泛的生物学效应。中介素是一种新型肽类激素，属降钙素基因相关肽(calcitonin gene related peptide, CGRP)超家族成员，具有介导血管舒张，心肌收缩，调节细胞增殖、肥大、迁移、凋亡等多种生物学效应。牛磺酸(Taurine, Tau)是人体组织细胞内含量最丰富的自由氨基酸，是体内重要的内源性抗损伤和细胞保护物质，具有广泛的生理和药理作用。 目的：研究牛磺酸对油酸所致急性肺损伤(ALI)大鼠的干预作用及其通过影响尾加压素Ⅱ(UⅡ)及中介素(IMD)合成与分泌，探讨其发挥肺保护作用的机制。 方法：采用制备油酸性急性肺损伤大鼠模型。实验动物大鼠分为3组：对照组(C组)，油酸损伤组(A组)，牛磺酸治疗组(T组)。分别于0h、6h、12h、24h四个时间点抽取动脉血2ml并取支气管肺泡灌洗液(BALF)4ml，测定动脉血氧分压(PaO2)，血浆及BALF中UⅡ、IMD浓度，测定肺湿干比(wet weight/dry weight W/D)进行统计学分析；肉眼观察肺脏大体标本；普通光镜及免疫组织化学检查肺组织病理变化；电镜观察肺脏组织超微结构。 结果： 1.三组大鼠PaO2在0h、6h、12h均有显著差异(P＜0.05)，6h、12h时T组高于A组。 2.三组肺组织W/D在0h、6h有差异(P＜0.05)，A组高于T组及C组(P＜0.05)。 3.三组血浆UⅡ在12h、24h时差异显著(P＜0.05)，A组高于C组及T组(P＜0.05)；三组BALF UⅡ在0h、6h、12h差异显著(P＜0.05)，A组高于T组及C组(P＜0.05)；A组血浆及BALF UⅡ在12h高于0h，6h及24h(P＜0.05)；T组血浆及BALF UⅡ在6h时最高(P＜0.05)。 4.三组血浆及BALF IMD在0h时比较有差异(P＜0.05)，A组高于T组及C组(P＜0.05)； A组血浆及BALF IMD在0h高于6h、12h、24h(P＜0.05)。 5.油酸致伤鼠肺肉眼见肺脏轻度肿胀，可见斑片状出血坏死。光镜观察：A组肺泡萎陷，肺间质水肿，弥漫性出血，肺泡腔内可见大量红细胞渗出和中性粒细胞浸润，血浆蛋白渗出增多。T组肺组织渗出减轻，中性粒细胞及红细胞渗出减少。 6.免疫组织化学染色结果显示各组大鼠支气管粘膜上皮细胞、平滑肌细胞，肺内血管内皮细胞、平滑肌细胞细胞膜及细胞质均有UⅡ与IMD阳性表达，A组与T组间表达无明显差异。 7.电镜观察：A组肺泡腔内出血，毛细血管内皮细胞损伤，基底膜破坏，Ⅱ型肺泡上皮细胞部分板层小体排空，肺泡间质中胶原增多。T组损伤减轻，基底膜完整，未见明显胶原纤维增生。 结论： 1.通过静脉注射油酸可成功制备急性肺损伤大鼠动物模型。 2.UⅡ在油酸致急性肺损伤致病过程中，可能通过扩张血管，增加血管通透性，发挥促进损伤作用。IMD在油酸致急性肺损伤致病过程中早期升高，可能通过稳定血管内皮细胞屏障功能、减轻血管渗出发挥其肺保护作用。 3.牛磺酸可以减轻油酸致大鼠急性肺损伤，其机制可能与促进UⅡ代谢降解，减轻毛细血管基底膜损伤后肺泡渗出有关，尚不能证明牛磺酸可通过促进IMD合成与分泌减轻肺损伤。
[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.
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