内毒素预处理对失血性休克大鼠肠道的保护作用  

Protective effect of LPS preconditioning on intestinal mucosa in a rat mode of hemorrhagic shock

作　　者：常瑞明[1] 常建星[1] 温立强[1] 余凯[1] 杨涛[1] 

机构地区：[1]中山大学孙逸仙纪念医院急诊科,广东 广州510120

出　　处：《中国急救医学》2015年第10期939-942,I0003,共5页Chinese Journal of Critical Care Medicine

基　　金：广东省自然科学基金

摘　　要：目的：探讨内毒素预处理对失血性休克造成大鼠肠道的损伤是否有保护作用及其可能机制。方法42只SD大鼠随机分为三组，即假手术对照组（Control组，n＝6）、失血性休克组（HS组，n＝18）及LPS预处理组（LPS＋HS组，n＝18），HS组和LPS＋HS组根据复苏后时间点不同分为三个亚组（3 h、6 h、12 h组，每组6只）。 Control组：大鼠只行插管处理；HS组：插管后大鼠通过颈总动脉放血使平均动脉压降至35～40 mm Hg，持续1 h后生理盐水复苏；LPS＋HS组：休克模型建立前，SD大鼠经腹腔注射高纯化的LPS（0．1 mg／kg），连续5 d，余步骤同休克组。分别在复苏后3h、6h和12 h处死动物，留取标本。按照肠黏膜损伤分级评估肠黏膜损伤程度；Western blot检测回肠黏膜TLR4的蛋白水平；ELISA法检测回肠黏膜和血清中TNF－α的表达。结果失血性休克组大鼠肠黏膜严重损伤，黏膜损伤积分、TLR4及TNF－α表达明显高于Control组（P＜0．01）。 LPS预处理明显减轻了肠黏膜的损伤程度，在复苏后3 h、6 h和12 h时间点，肠黏膜损伤积分及TNF－α表达明显低于盐水预处理（即HS）组（P＜0．01）；尽管黏膜TLR4在复苏后3 h高于Control组，但低于HS组，6 h和12 h的表达接近Control组。结论非致死量LPS预处理通过下调肠黏膜TLR4的表达，降低TRL4介导的肠黏膜炎症反应，从而减轻失血性休克大鼠的肠黏膜损伤。Objective To investigate whether lipopolysaccharide preconditioning is able to relieve the intestinal injury caused by hemorrhagic shock in a rat mode .Methods Forty-two male Sprague-Daweley rats were divided into three groups randomly , namely Control , hemorrhagic shock （HS） and LPS precondioning （LPS＋HS） group.The rats of Control group were only intubated , those of HS group were shed to a mean arterial pressure （ MAP） of 35-40 mmHg and maintained at this level for an hour and subsequently followed by resuscitation with 0.9% sodium chloride, and the animals of LPS＋HS group were received an dose with of sterilized purified Escherichia coli LPS intraperitoneally （0.1 mg/kg） for five consecutive days prior to hemorrhagic shock challenge .The distal segments of ileum were harvested at 3 hour, 6 hour and 12 hour after resuscitation .Intestinal mucosal damage was assessed according to the grading of intestinal tissue injury by the document .The protein concentration of TNF-αin small intestinal tissue and in serum were detected by ELISA; protein levels of TLR4 were determined with Western blot .Results Preconditioning with sublethal LPS remarkably alleviated the injury of intestinal mucosa in rats when subjected to shock challenge .The animals received pretreatment with LPS showed a prominently reduced intestinal mucosal damage score and TNF -αconcentration in intestinal mucosa compared to saline -pretreated animals （ P〈0.01 in 3 h, 6 h, 12 h time points, respectively ） .Although TLR4 was higher at 3 h group than Control group , it was lower significantly in＆amp;nbsp;LPS preconditioning rats than in saline preconditioning group .Moreover, the protein level of TLR4 at 6 h and 12 h group in LPS preconditioning rats were close to sham group .Conclusion These findings indicate that endotoxin tolerance by multiple exposure a low concentration of LPS has ability to alleviate intestinal mucosa injury in rats when received hemorrhagic shock .The mechanism may depend on decreased TLR4 expression

关 键 词：内毒素预处理 失血性休克 TLR4 TNF-Α 肠黏膜 

分 类 号：R657.305[医药卫生—外科学]