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中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2016, Vol. 11 ›› Issue (02) : 101 -106. doi: 10.3877/cma.j.issn.1673-9450.2016.02.005

所属专题： 文献；

论著

乌司他丁对中度烧冲复合伤大鼠肺损伤保护作用的研究
刘锐1, 王树明2, 李宗瑜1,†(), 张慧萍3, 曹卫红3, 胡森3, 盛志勇3   
  1. 1. 150040　哈尔滨市第五医院烧伤科
    2. 150040　哈尔滨，黑龙江中医药大学附属第一医院急诊科
    3. 100048　北京，解放军总医院第一附属医院烧伤研究所休克与多器官障碍实验室
  • 收稿日期:2016-01-11 出版日期:2016-04-01
  • 通信作者: 李宗瑜
  • 基金资助:
    全军"十二五"后勤科研计划课题资助项目(CKJ12J027); 哈尔滨市科技局科技创新人才研究专项资金项目(2015RAQYJ078)

Protective effect of ulinastatin on lung injury in rats with moderate burn-blast combined injury

Rui Liu1, Shuming Wang2, Zongyu Li1,†(), Huiping Zhang3, Weihong Cao3, Sen Hu3, Zhiyong Sheng3   

  1. 1. Department of Burns Surgery, the Fifth Hospital of Harbin, Harbin 150040, China
    2. Department of Emergency Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
    3. Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, the First Hospital Affiliated to General Hospital of People′s Liberation Army, Beijing 100048, China
  • Received:2016-01-11 Published:2016-04-01
  • Corresponding author: Zongyu Li
  • About author:
    Corresponding author: Li Zongyu, Email:
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刘锐, 王树明, 李宗瑜, 张慧萍, 曹卫红, 胡森, 盛志勇. 乌司他丁对中度烧冲复合伤大鼠肺损伤保护作用的研究[J]. 中华损伤与修复杂志(电子版), 2016, 11(02): 101-106.

Rui Liu, Shuming Wang, Zongyu Li, Huiping Zhang, Weihong Cao, Sen Hu, Zhiyong Sheng. Protective effect of ulinastatin on lung injury in rats with moderate burn-blast combined injury[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2016, 11(02): 101-106.

目的

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。

方法

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。

结果

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)。

结论

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。

关键词: 烧伤, 肺损伤, HSP70热休克蛋白类, 乙酰化组蛋白H3赖氨酸, 乌司他丁, 烧冲复合伤
Objective

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

Methods

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.

Results

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).

Conclusions

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.

Key words: Burns, Lung injury, HSP70 heat-shock proteins, Acetylation of histone H3 lysine 9, Ulinastatin, Burn-blast combined injury
图1 各组大鼠伤后6、24 h肺损伤评分
图2 ELISA法检测各组大鼠伤后6、24 h肺组织HSP70的含量
图3 Western-Blot检测各组大鼠伤后不同时间点肺组织保护性蛋白Ac-H3K9的蛋白表达情况
图4 干湿重法计算各组大鼠伤后6、24 h肺组织含水率
[1]
Chai JK, Cai JH, Deng HP, et al. Role of neutrophil elastase in lung injury induced by burn-blast combined injury in rats[J]. Burns, 2013, 39(4): 745-753.
[2]
Ebrahimi A, Kalantar Motamedi MH. Application of silver sulfadiazine cream with early surgical intervention in patients suffering from combined burn-blast injury facial tattoos[J]. Trauma Mon, 2012, 17(1): 255-258.
[3]
Mac Callum NS, Evans TW. Epidemiology of acute lung injury[J]. Curr Opin Crit Care, 2005, 11(1): 43-49.
[4]
Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury[J]. N Engl J Med, 2005, 353(16): 1685-1693.
[5]
刘锐，曹卫红，王树明，等. 开放爆炸环境下烧冲复合伤动物模型建立的研究[J/CD]. 中华损伤与修复杂志：电子版，2014, 9(6): 607-613.
[6]
Smith KM, Mozek JD, Simonton SC, et al. Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome[J]. Crit Care Med, 1997, 25(11): 1888-1897.
[7]
Luo HM, Hu S, Bai HY, et al. Valproic acid treatment attenuates caspase-3 activation and improves survival after lethal burn injury in a rodent model[J]. J Burn Care Res, 2014, 35(2): e93-e98.
[8]
Li X, Hammer AM, Rendon JL, et al. Intestine immune homeostasis after alcohol and burn injury[J]. Shock, 2015, 43(6): 540-548.
[9]
王一贺，杨红明，胡泉，等. 西维来司钠对重度烧冲复合伤犬急性肺损伤的影响[J]. 中华烧伤杂志，2014, 30(2): 158-165.
[10]
Pugia MJ, Valdes R Jr, Jortani SA. Bikunin (urinary trypsin inhibitor): structure, biological relevance, and measurement[J]. Adv Clin Chem, 2007, 44: 223-245.
[11]
Gao C, Liu Y, Ma L, et al. Protective effects of ulinastatin on pulmonary damage in rats following scald injury[J]. Burns, 2012, 38(7): 1027-1034.
[12]
Luo HM, Du MH, Lin ZL, et al. Ulinastatin suppresses burn-induced lipid peroxidation and reduces fluid requirements in a Swine model[J]. Oxid Med Cell Longev, 2013, 2013: 904370.
[13]
Sio SW, Moochhala S, Lu J, et al. Early protection from burn-induced acute lung injury by deletion of preprotachykinin-A gene[J]. Am J Respir Crit Care Med, 2010, 181(1): 36-46.
[14]
刘锐，王树明，曹卫红，等. 乌司他丁对中度烧冲复合伤大鼠肺炎症介质和血管通透性的影响[J/CD]. 中华损伤与修复杂志：电子版，2015, 10(2): 132-136.
[15]
刘锐，王晓娜，王树明，等. 乌司他丁对50%总体表面积烫伤大鼠心肌保护作用的研究[J]. 中国急救医学，2015, 35(5): 455-458.
[16]
刘锐，王树明，曹卫红，等. 乌司他丁对烫伤大鼠脑组织的保护作用及其可能机制[J]. 中华医学杂志，2015, 95(36): 2952-2954.
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