研究乌司他丁对中度烧冲复合伤大鼠肺组织保护作用及其可能机制。

120只雄性SD大鼠按随机数字表法分为4组：假伤＋0.9%氯化钠溶液组(简称SS组，n＝20)、假伤＋乌司他丁组(简称SU组，n＝20)、烧冲复合伤＋0.9%氯化钠溶液组(简称BBS组，n＝40)和烧冲复合伤＋乌司他丁组(简称BBU组，n＝40)。BBS组和BBU组均制成25%TBSA深Ⅱ度烧伤＋中度冲击伤的中度烧冲复合伤模型，SS组与SU组大鼠麻醉后，除不致伤外其他干预方法同烧冲复合伤模型制作。伤后即刻，大鼠尾静脉分别对应给予注射0.9%氯化钠溶液和乌司他丁4万U/kg。各组大鼠分别于伤后6、24 h以腹主动脉抽血法处死(BBS、BBU组每时刻点各随机选取20只)后取肺组织观察病理学变化并进行肺损伤评分，采用ELISA法检测肺组织热休克蛋白70(HSP70)的含量，Western Blot试验测定肺组织中乙酰化组蛋白H3赖氨酸9(Ac-H3K9)相对表达量，干湿重法测定肺组织含水率。

伤后6 h，BBS组、BBU组大鼠肺损伤评分分别为(5.82±0.37)、(4.20±0.32)分，肺组织保护性蛋白HSP70含量分别为(205.0±2.3)、(220.0±2.4) pg/mL，Ac-H3K9的相对表达量分别为0.68±0.13、1.45±0.12，肺组织含水率分别为(85.30±2.13)%、(82.70±1.57)%；伤后24 h，BBS组、BBU组大鼠肺损伤评分分别为(8.25±0.42)、(6.11±0.31)分，HSP70含量分别为(221.0±2.4)、(226.0±2.7)pg/mL，Ac-H3K9的相对表达量分别为1.59±0.17、1.78±0.15，肺组织含水率分别为(82.80±1.57)%、(80.20±0.32)%。伤后6、24 h，BBS组与BBU组肺损伤评分比较差异均有统计学意义(t＝6.132、6.791，P＝0.026、0.016)，肺组织含水率比较差异均有统计学意义(t＝6.123、5.894，P＝0.034、0.019)，伤后6 h，两组HSP70、Ac-H3K9表达水平比较差异均有统计学意义(t＝ 2.795、3.165，P＝0.031、0.028)，伤后24 h，两组HSP70、Ac-H3K9表达水平比较差异均无统计学意义(t＝ 2.143、3.154，P值均大于0.05)。伤后6、24 h，同一观测时间点BBS组与BBU组肺损伤评分、HSP70、Ac-H3K9表达水平、肺组织含水率分别与SS组、SU组比较，差异均有统计学意义(P值均小于0.05)。

乌司他丁能减轻大鼠烧冲复合伤早期肺组织水肿和病理损害，其机制可能与乌司他丁能增加肺组织保护性蛋白的表达、提高大鼠对损伤的耐受力有关。

To investigate the protective effects of ulinastatin on lung tissue in rats following moderate burn-blast combined injury and its mechanism.

One hundred and twenty male Sprague-Dawley rats were randomly divided into four groups: sham+ saline group (group SS, n=20), sham+ ulinastatin (group SU, n=20), burn-blast combined injury+ saline(group BBS, n=40) and burn-blast combined injury+ ulinastatin (group BBU, n=40). Rats in the group BBS and BBU were subjected to a model with moderate burn-blast combined injury. Rats in the group SS and SU were anesthetized, in addition to no hurt, other interventions the same to the model with moderate burn-blast combined injury. Immediately after injury rats were intravenously given either 1 mL saline in group SS and BBS or 1 mL saline containing ulinastatin(40000 U/kg) in group SU and BBU. The rats were sacrificed at the end of experiment and observed the pathological changes of lung tissue in rates by optical microscope. Lung tissues were harvested for the measurement of acetylated histone H3 by Western Blot and heat shock protein 70 by enzyme-linked immuno sorbent assay. The rates of tissue water content in lung were determined by the dry/wet weight.

At 6 h after injury, the lung injury score of group BBU and group BBS were (5.82±0.37) points, (4.20±0.32) points, the expression of heat shock protein 70 in group BBU and group BBS were (205.0±2.3) pg/mL, (220.0±2.4) pg/mL, the expression of acetylation histone H3 Lys9 in group BBU and group BBS were 0.68±0.13, 1.45±0.12, the water content of lung tissue in group BBS and group BBU were (85.30±2.13)%, (82.80±1.57)% respectively. At 24 h after injury, the lung injury score of group BBU and group BBS were (8.25±0.42), (6.11±0.31) points, the expression of heat shock protein 70 in group BBU and group BBS were (221.0±2.4) pg/mL, (226.0±2.7) pg/mL, the expression of acetylation histone H3 Lys9 in group BBU and group BBS were 1.59±0.17, 1.78±0.15, the water content of lung tissue in group BBS and group BBU were (85.80±1.57)%, (80.20±0.32)% respectively. The lung injury scores of group BBS and group BBU were significantly different at 6 h and 24 h after injury (t=6.132, 6.791, P=0.026, 0.016), the water content of lung tissue in group BBS and group BBU were significantly different at 6 h and 24 h after injury (t=6.123, 5.894, P=0.034, 0.019), the difference of the expression of heat shock protein 70 and acetylation histone H3 Lys9 at 6 h after injury between group BBS and group BBU was statistically significant (t=2.795, 3.165, P=0.031, 0.028), while the expression of heat shock protein 70 and acetylation histone H3 Lys9 had no significant difference at 24 h after injury (t=2.143, 3.154, all P values were greater than 0.05). At 6 h and 24 h after injury, the lung injury scores, the water content of lung tissue, the expression of heat shock protein 70 and acetylation histone H3 Lys9 of the group BBS and group BBU had significant difference at the same time point compared with group SS and group SU (all P values were less than 0.05).

The results indicated that ulinastatin significantly alleviated burn-blast combined injury-induced lung edema and pathologic changes. These protective effects may be due to high expressions of protective proteins and increased tolerance to burn-blast combined injury.