蛋白酶抑制剂乌司他丁在兔肺缺血再灌注损伤中的保护作用

发布时间：2018-08-26 07:35

【摘要】：背景与目的乌司他丁(ulinastatin, ULI)是1909年由Beuer和Reich从男性尿液中分离纯化的胰蛋白酶抑制剂,为糖蛋白,含143个氨基酸,1985年由日本首先开发上市,其在临床研究中显示：当人体受到各种刺激时,如创伤、休克、手术、感染等,人体尿液中UTI活性增强,但随着机体的恢复,浓度又逐渐回复正常。这表明UTI具有抵抗外来刺激,减少机体的损伤,维持人体内环境平衡的作用。目前国内外学者普遍认为.当机体受到各种因素刺激时,如创伤、手术、严重感染、休克、重症胰腺炎及缺血再灌注损伤等,便可以形成失控的瀑布样全身性炎症反应,即全身性炎症反应综合征(SIRS),在这种状态下,即使原发致病因素消除或减弱,炎症反应仍可继续,并可最终导致多器官功能障碍综合征(MODS)的发生。其中呼吸功能障碍在多器官功能障碍综合征中发生率较高,出现时间早,一般在发病后24～72h,临床表现为急性肺损伤(AU)或急性呼吸窘迫综合征(ARDS),病死率高达40%～80%。急性肺损伤的治疗目标包括：治疗基础病和防治并发症,改善肺的氧合功能,纠正缺氧,基本生命支持,保护器官功能等。急性肺损伤的成功治疗必须遵循严密监护与重症医学紧密结合的原则。为此,我们应用UTI作为对急性肺损伤肺保护的治疗策略,探讨乌司他丁对活体肺缺血再灌注损伤的保护作用。材料与方法将20只新西兰大白兔随机分成缺血再灌注损伤组(A组)和乌司他丁组(B组),B组阻断前给乌司他丁(10 000U/kg体重)。两组阻断2h和再灌注1h后采血检测血气、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。摘取左肺测定湿干重比(W/B)和病理学检查。结果阻断2h后,两组血氧分压(PO2)接近；恢复灌注1h后,B组PO2高于A组(77.61±5.04)mmHg(1 mmHg=0.133 kPa)和(100.85±6.73)mmHg;TNF-α值(A值),A组各时段均显著高于B组(254.02±14.31和504.02±33.52比148.63±21.06和160.54±16.93)；A组肺湿干重比高于B组；肺外观苍白肿胀。结论乌司他丁能保护在体肺缺血再灌注中肺组织结构的损伤。
[Abstract]:Background & objective Ulinastatin (ulinastatin, ULI), a glycoprotein containing 143 amino acids, was isolated and purified from male urine by Beuer and Reich in 1909. It was first developed and marketed in Japan in 1985. The clinical research shows that when the human body is stimulated by various kinds of stimuli, such as trauma, shock, surgery, infection and so on, the activity of UTI in human urine is increased, but with the recovery of the body, the concentration gradually returns to normal. This suggests that UTI can resist external stimuli, reduce body damage and maintain the balance of human environment. At present, domestic and foreign scholars generally think. When the body is stimulated by a variety of factors, such as trauma, surgery, severe infection, shock, severe pancreatitis, and ischemia-reperfusion injury, it can form a runaway cascade of systemic inflammation. That is, in this condition, the inflammatory response of systemic inflammatory response syndrome (SIRS),) can continue even if the primary pathogenic factors are eliminated or weakened, and can eventually lead to the occurrence of multiple organ dysfunction syndrome (MODS). The incidence of respiratory dysfunction in multiple organ dysfunction syndrome was high and the onset time was early. The clinical manifestation of respiratory dysfunction was acute lung injury (AU) or acute respiratory distress syndrome (ARDS),). The mortality rate was as high as 40% and 80% after the onset of acute lung injury (AU) or acute respiratory distress syndrome (ARDS),). The treatment goals of acute lung injury include treating basic diseases and preventing complications, improving oxygenation function of lung, correcting hypoxia, supporting basic life, protecting organ function and so on. The successful treatment of acute lung injury must follow the principle of close combination of intensive care and intensive medicine. Therefore, we use UTI as a therapeutic strategy for acute lung injury and explore the protective effect of ulinastatin on lung ischemia-reperfusion injury in vivo. Materials and methods Twenty New Zealand white rabbits were randomly divided into two groups: ischemia reperfusion injury group (group A) and ulinastatin group (group B). They were given ulinastatin (10 000U/kg body weight) before occlusion. Blood gas, interleukin-6 (IL-6) and tumor necrosis factor- 伪 (TNF- 伪) were measured at 2 h after occlusion and 1 h after reperfusion. The left lung was removed for wet dry weight ratio (W / B) and pathological examination. Results the partial pressure of oxygen (PO2) in two groups was close to that in group A 2 h after reperfusion, the PO2 of group B was higher than that of group A (77.61 卤5.04) mmHg (1 mmHg=0.133 kPa) and group A (100.85 卤6.73) mmHg;TNF- 伪 (A value) 1 h after reperfusion, and the lung wet dry weight ratio of group A was significantly higher than that of group B (254.02 卤14.31 vs 504.02 卤33.52 vs 148.63 卤21.06 and 160.54 卤16.93). The lung looks pale and swollen. Conclusion Ulinastatin can protect lung tissue from injury during ischemia reperfusion in vivo.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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