Wang S Y, Li Z J, Wang X, Li W F, Lin Z F
Department of Emergency and Critical Care Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
Department of Anesthesiology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
Genet Mol Res. 2015 Apr 30;14(2):4344-53. doi: 10.4238/2015.April.30.7.
The aim of this study was to investigate the influence of ulinastatin (UTI) on high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression in acute lung injury (ALI) rats with sepsis caused by cecal ligation and puncture (CLP) surgery, as well as to examine the underlying biological mechanism. Thirty rats were randomly and evenly divided into sham (control), CLP, and CLP + UTI groups. Thirty minutes after the surgery, the rats in the CLP + UTI group received UTI via the caudal vein, while normal saline was administered to rats in the other groups. Blood, lung tissues, and bronchoalveolar lavage fluid (BALF) were collected at different time points (6, 12, 24, and 48 h) after surgery for determination of related indicators. Compared with the CLP group, rats in the CLP + UTI group exhibited higher seven day survival rates, less lung injury, and decreased HMGB1 expression in the lung tissue, serum, and BALF. In addition, the levels of TNF-α and IL-6 at 24 h in the CLP + UTI group were markedly lower than those in the CLP group. These results suggest that by deregulation, UTI might decrease the lung injury and increase the survival time of ALI rats by downregulating HMGB1 expression as well as by inhibiting TNF-α and IL-6 levels in serum and BALF.
本研究旨在探讨乌司他丁（UTI）对盲肠结扎穿孔（CLP）手术所致脓毒症急性肺损伤（ALI）大鼠高迁移率族蛋白B1（HMGB1）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6表达的影响，并探讨其潜在的生物学机制。30只大鼠随机均分为假手术（对照）组、CLP组和CLP + UTI组。术后30分钟，CLP + UTI组大鼠经尾静脉注射UTI，其他组大鼠给予生理盐水。术后不同时间点（6、12、24和48小时）采集血液、肺组织和支气管肺泡灌洗液（BALF），测定相关指标。与CLP组相比，CLP + UTI组大鼠7天生存率更高，肺损伤更轻，肺组织、血清和BALF中HMGB1表达降低。此外，CLP + UTI组24小时时TNF-α和IL-6水平明显低于CLP组。这些结果表明，UTI可能通过下调HMGB1表达以及抑制血清和BALF中TNF-α和IL-6水平，减轻肺损伤，延长ALI大鼠的生存时间。
