硫辛酸对内毒素诱导的大鼠急性肺损伤的保护作用  

Protective Effects of Lipoic Acid in Acute Lung Injury Rats Caused by Lipopolysaccharide

作　　者：田金飞[1] 权伟合[1] 向小卫[1] 阮班银 汤彦[2] 童朝阳[3] 

机构地区：[1]湖北医药学院附属东风医院重症监护室,湖北十堰442008 [2]复旦大学附属中山医院青浦分院急诊科,上海201700 [3]复旦大学附属中山医院急诊科,上海200032

出　　处：《中国临床医学》2013年第5期628-631,共4页Chinese Journal of Clinical Medicine

基　　金：上海市青浦区科委基金项目(编号:2011-29)

摘　　要：目的:以内毒素(1ipopolysaccharide,LPS)诱导法建立大鼠急性肺损伤(acutelung i njury,ALI)模型,探讨不同剂量的硫辛酸(1ipoic acid,LA)处理对大鼠ALI的保护作用。方法:选择健康SD大鼠90只,其中72只SD大鼠腹腔注射LPS 25 mg/kg,构建大鼠ALI模型,再按不同干预方法将72只大鼠分为LA阴性对照组(腹腔注射等量0.9%氯化钠液)、LA大剂量组[腹腔注射LA 120 mg/(kg·d)]、LA中剂量组[腹腔注射LA 60 mg/(kg·d)]、LA小剂量组[腹腔注射LA 30 mg/(kg·d)],每组18只;其余18只大鼠,仅腹腔注射等量0.9%氯化钠液(正常组)。检测各组大鼠处理24、48、72 h后肺组织中核因子κB(NF-kappa B,NF-κB)、白细胞介素1(interleukin 1,IL-1)、NO合成酶(NO synthetase,NOS)、NO、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的水平。结果:LPS诱导后,LA阴性对照组大鼠肺组织中NF-κB、IL-1、NOS、NO)、TNF-α在72 h时最高。与正常组大鼠比较,其余各组NOS、NO、TNF-α的水平均较高,差异有统计学意义(P<0.05);与LA阴性对照组比较,处理24、48、72 h后LA大剂量组IL-1、NF-κB、NOS、NO、TNF-α的水平明显下降(P均<0.05),LA中剂量组在处理24 h后的NOS、NO水平以及处理72 h的NO水平也明显下降(P均<0.05)。结论:LA对ALI大鼠的治疗效果以大剂量组最为明显,其机制可能与LA抑制NF-κB激活以及下调肺组织中IL-1、NOS、NO、TNF-a的表达有关。Objective：To establish acute lung injury （ALI） rat model with lipopolysaccharide （LPS）,and to explore the protective effect of different dosage of lipoic acid （LA） in rat ALI.Methods：A total of 90 healthy SD rats were enrolled.Among them,72 rats were intraperitoneally injected with 25 mg/kg LPS to induce rat ALI model and according to different intervention methods,those 72 rats were divided into negative control group （intraperitoneal injection with saline solution）,LA highdose group （intraperitoneal injection with LA,120 mg/（kg · d）,LA middle-dose group （intraperitoneal injection with LA,60 mg/（kg · d） and LA low-dose group （intraperitoneal injection with LA,30 mg/（kg · d）,with 18 rats in each group; the other 18 rats were intraperitoneally injected with saline solution（normal group）.The levels of NF-kappa B （NF-κB）,tumor necrosis factor-α （TNF-α）,NO synthetase （NOS）,NO and interleukin 1 （IL-1） in lung tissues of each group were detected after treatment for 24,48,72 h.Results：The levels of NF-kappa B,TNF-α,NOS,NO and IL-1 in the lung tissues showed the highest at 72 h after LPS induction.Compared with the normal group,the levels of NOS,NO and TNF-α in the other groups were increased,and the difference had statistical significance （P＜0.05）.Compared with those in the LA negative group,the levels of IL-1,NF-κb,NOS,NO and TNF-α in LA high-dose group were significantly decreased after treatment for 24,48 and 72 h （P all ＜0.05）.Moreover,the levels of NOS and NO after treatment for 24 h and the level of NO after treatment for 72 h in LA middle-dose group were significantly decreased （all P＜0.05）.Conclusions：LA High-dose group shows highest protective effect in rat ALI model.The underlying mechanism may be correlated with the down-regulation of the expressions of IL-1,NOS,NO and TNF-α through NF-κB activation inhibited by LA.

关 键 词：硫辛酸 内毒素 急性肺损伤 大鼠 

分 类 号：R643[医药卫生—外科学]