烫伤后脓毒症大鼠肺组织炎症反应和自噬与NOD2信号通路的关系  

Relationship between inflammatory responses and autophagy in lung tissues after scald and NOD2 signaling pathway in septic rats

作　　者：张颖[1] 颜学滔[2] 梁辉[1] 宋学敏[1] 张宗泽[1] 王焱林[1] 王洪雨 杨旭明[1] 李卉[1] 李心怡[1] 陈凯[1] Zhang Ying;Yan Xuetao;Liang Hui;Song Xuemin;Zhang Zongze;Wang Yanlin;Wang Hongyu;Yang Xuming;Li Hal;Li Xinyi;Chen Kai(Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China;Department of Anesthesiology, Baoan District Maternal and Child Health Care Hospital of Shenzhen, Shenzhen 518100, Chin)

机构地区：[1]武汉大学中南医院麻醉科,430071 [2]深圳市宝安区妇幼保健院麻醉科,518100

出　　处：《中华麻醉学杂志》2017年第12期1533-1536,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81101449,81571924）

摘　　要：目的评价烫伤后脓毒症大鼠肺组织炎症反应和自噬与Nod样受体2（NOD2）信号通路的关系。方法SPF级健康雄性SD大鼠20只，体重200～250 g，采用随机数字表法分为2组（n＝10）：对照组（C组）和烫伤后脓毒症组（SS组）。于20%总体表面积Ⅲ度烫伤（背部皮肤浸入99～100 ℃热水中，持续12 s）后24 h静脉注射胞壁酰二肽5 mg/kg的方法制备烫伤后脓毒症模型。C组于20 ℃水中假烫伤后24 h静脉注射生理盐水1 ml。SS组于静脉注射胞壁酰二肽后6 h、C组于注射生理盐水后6 h时，取动脉血标本，采用ELISA法检测血清TNF-α和IL-6浓度，随后取肺组织，测定髓过氧化物酶（MPO）活性，采用RT-PCR法检测肺组织NOD 2 mRNA的表达，采用Western blot法检测受体相互作用蛋白-2（RICK）、NF-κBp65和微管相关蛋白1轻链3Ⅰ和Ⅱ（LC3Ⅰ、LC3Ⅱ）的表达。计算LC3Ⅰ与LC3Ⅱ的比值（LC3Ⅰ/Ⅱ）。结果与C组比较，SS组肺组织NOD2 mRNA、RICK、NF-κBp65表达上调，LC3Ⅰ/Ⅱ、血清TNF-α和IL-6浓度升高（P〈0.05）。结论大鼠烫伤后脓毒症时肺组织炎症反应和自噬水平增强的机制可能与NOD2信号通路激活有关。Objective To evaluate the relationship between inflammatory responses and autophagy in lung tissues after scald and nucleotide-binding oligomerization domain-containing protein 2（NOD2）signaling pathway in septic rats.Methods Twenty SPF healthy male Sprague-Dawley rats, weighing 200-250 g, were divided into control group（group C, n=10） and sepsis after scald group（group SS, n=10）using a random number table.The rats were subjected to a third-degree scald burn covering 20% of total body surface area（body surface was shaved and then exposed to 99-100 ℃ water for 12 s）, and 24 h later muramyldipeptide 5 mg/kg was intravenously injected to induce sepsis.The rats were only exposed to 20 ℃ water, and 24 h later normal saline 1 ml was given instead in group C. At 6 h after muramyldipeptide injection in group SS and at 6 h after normal saline injection in group C, arterial blood samples were collected for determination of serum tumor necrosis factor-α and interleukin-6 concentrations by enzyme-linked immunosorbent assay.Then rats were sacrificed and lungs were removed for measurement of activity of myeloperoxidase, NOD2 mRNA expression（using real-time polymerase chain reaction）and expression of receptor interacting protein 2, nuclear factor kappa Bp65 and microtubule-associated protein 1 light chain 3Ⅰ（LC3Ⅰ）and LC3Ⅱ in lung tissues（by Western blot）. The LC3Ⅱ/Ⅰratio was calculated.Results Compared with group C, the expression of NOD2 mRNA, receptor interacting protein 2 and nuclear factor kappa Bp65 was significantly up-regulated, and the LC3Ⅱ/Ⅰratio and serum tumor necrosis factor-α and interleukin-6 concentrations were increased in group SS（P〈0.05）.Conclusion The mechanism underlying enhanced inflammatory responses and autophagy in lung tissues during sepsis after scald may be related to activation of NOD2 signaling pathway in rats.

关 键 词：烧伤 脓毒症 Nod2信号接头蛋白质 自噬 炎症 肺 

分 类 号：R459.7[医药卫生—急诊医学]