不同剂量乌司他丁对急性肺损伤大鼠MMP-9等炎症因子调控的研究

目的：通过盲肠结扎穿刺（CLP）手术致大鼠脓毒性急性肺损伤（ALI）,研究并比较不同剂量的乌司他丁（UTI）对基质金属蛋白酶（MMP-9）及TNF-α、IL-6、IL-8、IL-10水平变化的影响并探讨UTI的作用机制。方法：将84只SD大鼠随机分为CLP手术组（ALI组）、乌司他丁5万U/kg治疗组（UTI1组）、乌司他丁10万U/kg治疗组（UTI2组）。UTI治疗组在手术完成后立即给予对应剂量的UTI。动物成模后在各对应时间点取材,检测各组生存率、肺湿重系数、肺组织病理,MMP-9及TNF-α、IL-6、IL-8、IL-10血清水平。结果：在使用UTI干预后大鼠肺组织损伤有所减轻,生存率尚无明显变化。各组炎症介质均出现下降,MMP-9及IL-8下降最为显著（P〈0.01）。结论：UTI通过广泛抑制炎症因子水平对肺损伤起保护作用,UTI的肺保护中MMP-9及IL-8可能比TNF-α、IL-6等炎症因子的作用更重要。超大剂量的UTI可以进一步下调炎症因子水平,但尚无明确证据说明使用UTI可以改善大鼠生存率。

The study on regulation of MMP-9 and other inflammatory factors in rat acute lung injury by different doses of Ulinastatin

Objective：To research and compare MMP-9 and TNF-α,IL-6,IL-8,IL-10 levels by different doses of UTI and explore the role of UTI mechanism with acute lung injury induced through sepsis by using method of cecal ligation and puncture.Methods：84 SD rats were randomly divided into CLP group and UTI 5×10 4 U/kg group（UTI1）,UTI 10×10 4 U/kg group（UTI2）.The corresponding dose of UTI was given immediately after surgery in UTI treatment group.Survival rate,lung wet weight index,pathology score of lung,MMP-9,TNF-α,IL-6,IL-8 and IL-10 serum levels were detected at every time point.Results：Lung injury alleviated after using the UTI intervention,significant survival rate change did not ap peared.Inflammatory mediators in each group were declining,MMP-9 and IL-8 decreased the most significant（P0.01）.Conclusion：UTI plays a protective role against lung injury through inhibiting by a wide range of inflammatory factors,MMP-9 and IL-8 might be more important than TNF-α,IL-6 and other inflammatory factors in UTI lung protection.Large doses of UTI could further reduce levels of inflammatory factors,but there is no clear evidence that UTI could improve the rat survival rate.