肝脏p38MAPK/NF-κB通路在大鼠烧伤休克期切痂以减轻炎症反应中的作用  

Role of liver p38 mitogen-activated protein kinase/nuclear factor-κB pathway in eschar excision during burn shock stage for reducing the inflammatory response in rats

作　　者：段建兴 刘文军[1] 曾跃勤 张高飞 王迪 李佳美 娄涵潇 Duan Jianxing;Liu Wenjun;Zeng Yueqin;Zhang Gaofei;Wang Di;Li Jiamei;Lou Hanxiao(Department of Burn,Second Affiliated Hospital of Kunming Medical University,Kunming,Yunnan 650500,China;Molecular Clinical Medical Institute,Kunming Medical University,Kunming,Yunnan 650500,China)

机构地区：[1]昆明医科大学第二附属医院烧伤科,云南昆明650500 [2]昆明医科大学分子临床医学研究院,云南昆明650500

出　　处：《感染．炎症．修复》2020年第1期16-21,共6页Infection Inflammation Repair

基　　金：国家自然科学基金资助项目(81660319);昆明医科大学2019年研究生创新基金项目(2019S042)。

摘　　要：目的:观察大鼠烧伤休克期切痂后炎症因子的变化规律及炎症的作用机制。方法:Wistar大鼠作为异体皮供体。SD大鼠水浴法复制30%TBSAⅢ度烫伤模型。动物随机分为模型组、切痂组(烫伤后12 h切痂,覆盖异体皮)、假手术组(假烫伤,伤后12 h模拟切痂覆盖自体皮)。各组于伤后24、48、72和96 h(模型组另观察伤后12 h)处死大鼠(每个时相点5只动物),取血和肝组织,酶联免疫吸附法检测血清中的炎症因子、Western blot方法检测肝脏p38丝裂原活化蛋白激酶(MAPK)/核因子-κB(NF-κB)通路相关蛋白变化水平。结果:模型组血清中的内毒素结合蛋白(LBP)、高迁移率族蛋白B1(HMGB1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和IL-10水平约在12~48 h到达高峰后逐渐平稳,HMGB1逐渐增高,并在96 h到达高峰(P<0.01)。切痂组及假手术组在同一时相点与模型组比较,除了LBP外,其他炎症因子均呈明显下降(P<0.01或P<0.05),肝脏p38MAPK水平变化无明显差异,磷酸化p38MAPK及磷酸化NF-κB明显下降(P<0.05或P<0.01);切痂组组内比较,以上炎症因子及肝脏p38MAPK和NF-κB磷酸化水平与24 h比较呈明显的下降趋势。结论:休克期切痂能够减少烧伤后炎症因子的活化,并可能通过p38MAPK/NF-κB炎症通路来减少炎症反应;切痂后全身炎症反应水平呈现更快下降的趋势。Objective:To observe the changes of inflammatory factors after eschar excision during burn shock stage for exploring the mechanism of inflammation in rats.Methods:Wistar rats were used as allogeneic skin donors.Full thickness scald of 30%total body surface area(TBSA)burn model was replicated using immersion method in SD rats.The rats were randomly divided into model group(replicating scald burn model),eschar excision group(excising eschars 12 hours after scald and covered with allogeneic skin),sham operation group(sham-scald,sham excising eschars and covered with autologous skin).The rats were sacrificed at 24,48,72 and 96 hours(12 hours additionally in model group,n=5),blood and liver tissue were sampled.The inflammatory factors in the serum were detected by enzyme linked immunoadsorbent assay,and the levels of p38 mitogen-activated protein kinase(MAPK)/nuclear factor-κB(NF-κB)pathway-related proteins in the liver were detected by Western blotting.Results:The levels of endotoxin binding protein(LBP),interleukin(IL)-6,tumor necrosis factor(TNF)-αand IL-10 in the serum of the model group gradually stabilized after reaching the peak at 12-48 hours,and HMGB-1 gradually increased and reached the peak at 96 hours(P<0.01).Compared with the model group,the eschar excision group and the sham operation group showed a significant decrease in the inflammatory factors(P<0.05 or P<0.01)except LBP,and there was no significant difference in liver p38MAPK,but phosphorylation of p38MAPK and phosphorylation of NF-κB was significantly decreased(P<0.05 or P<0.01).The above inflammatory factors and liver protein phosphorylation levels were significantly decreased compared with 24 hours in the eschar excision grafting group.Conclusions:Eschar excision during burn shock stage can reduce the activation of inflammatory cytokines in burns by the p38MAPK/NF-κB inflammatory pathway,and the level of systemic inflammatory response after escharectomy shows a faster reduction trend in rats.

关 键 词：烧伤 焦痂切除术 炎症因子 P38丝裂原活化蛋白激酶 核因子-ΚB 

分 类 号：R644[医药卫生—外科学]