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目的:探讨不同剂量乌司他丁(UTI)对爆炸致急性肺损伤(ALI)的治疗效果,并探讨其作用机制。方法:制作爆炸致家兔急性肺损伤模型,选择家兔40只,随机分为5组,每组8只:空白对照组(N组)、模型组(ALI组)和低、中、高剂量UTI干预组(L/M/H组)。造模完成后,L/M/H组分别注射(2.5,5,10×104U·kg-1)UTI溶液,N组与ALI组静脉注射等量0.9%Na Cl溶液。24 h后取支气管肺泡灌洗液(BALF)、血液及肺组织,用ELISA方法检定BALF及血清中TNF-α,IL-6的含量,蛋白印迹法和RT-PCR方法测定肺组织MMP-9蛋白和mRNA的表达水平,测定肺湿干重比,光镜下观察肺组织病理学变化。结果:ALI组湿干重比(W/D),TNF-α,IL-6以及基质金属蛋白酶-9(MMP-9)表达量均较N组升高(P<0.05),L/M/H组的W/D,TNF-α,IL-6表达量均较ALI组降低(P<0.05),以H组最为显著(P<0.05);肺病理检查显示M和H组肺组织肺水肿、炎症反应等较ALI组明显减轻。结论:乌司他丁可通过降低MMP-9的表达,抑制TNF-α,IL-6细胞因子的产生、释放,减轻爆炸致急性肺损伤的肺部损伤,高剂量干预效果更显著,UTI可能成为临床救治急性肺损伤的潜在用药之一。
Objective: To investigate the therapeutic effect of different doses of ulinastatin (UTI) on acute lung injury caused by explosion (ALI) and to explore its mechanism. Methods: A total of 40 rabbits were randomly divided into 5 groups (n = 8): blank control group (N group), model group (ALI group) and low, medium and high doses UTI intervention group (L / M / H group). After modeling, UTI solution (2.5, 5, 10 × 104 U · kg-1) was injected into L / M / H group, and 0.9% NaCl solution was intravenously injected into N and ALI groups. Bronchoalveolar lavage fluid (BALF), blood and lung tissue were collected 24 hours later. The contents of TNF-α and IL-6 in BALF and serum were determined by ELISA. The expression of MMP-9 in lung tissue was detected by Western blot and RT- Protein and mRNA expression levels were measured lung wet weight ratio, lung histopathological changes observed under light microscope. Results: The expression of W / D, TNF-α, IL-6 and MMP-9 in ALI group were higher than those in N group (P <0.05) The expression of W / D, TNF-α and IL-6 in H group were significantly lower than those in ALI group (P <0.05), and H group was the highest (P <0.05). Lung pathological examination showed pulmonary edema , Inflammatory response than ALI group significantly reduced. Conclusion: Ulinastatin can inhibit the production and release of TNF-α and IL-6 cytokines by reducing the expression of MMP-9 and relieve the lung injury caused by explosion-induced acute lung injury. The effect of high-dose intervention is more obvious. UTI may be Become one of the potential clinical treatment of acute lung injury.