Toll样受体4在内毒素和“两次打击”致小鼠急性肺损伤中作用的比较  

Comparison of roles of Toll-like receptor-4 in acute lung injury induced by lipopolysaccharide and by hem- orrhagic shock and resuscitation and llpopolysaccharide （＂ two-hit＂） in mice

作　　者：陈畅[1] 张帆[2] 张宗泽[1] 彭勉[1] 王焱林[1] 

机构地区：[1]武汉大学医学院附属中南医院麻醉科,430071 [2]武汉大学医学院附属人民医院麻醉科,430071

出　　处：《中华麻醉学杂志》2011年第8期974-976,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000318）;武汉大学青年教师资助项目（4101003）

摘　　要：目的比较Toll样受体4（TLR-4）在内毒素（IJPs）和“两次打击”致小鼠急性肺损伤（ALI）中的作用。方法雄性野生型小鼠C3H／HeN和TLR-4基因突变型小鼠C3H／HeJ各36只，采用随机数字表法，将2种小鼠各随机分为2组（n=18），假手术／LPS组（S／LPS组）只进行手术操作而不实施放血诱导休克，失血性休克复苏／LPS组（HSR／LPS组）制备失血性休克复苏模型。复苏后24h时2组气管内滴注LPS30μg／kg。分别于给予LPS后即刻（T1）、3h（R）和6h（B）时取6只小鼠，采集动脉血样，测定PaO2，然后处死小鼠，取肺组织，计算肺组织湿／干重比，并测定髓过氧化物酶（MP0）活性、IL-10和IL-6的含量。以T1时均数作为基础值，计算T2,3时各指标的变化率。结果与S／LPS组比较，C3H／HeN小鼠的HSR／LPS组T2，3时PaO2变化率降低，肺组织W／D比、MPO、IL-6和IL-10的变化率升高（P〈0．05或0．01），C3H／HeJ小鼠的HSR／LPS组L时PaO2变化率降低，肺组织W／D比、MPO、IL-6和IL-10的变化率升高（P〈0．05或0．01），T1时上述指标差异无统计学意义（P〉0．05）。结论与LPS致小鼠Au中的作用比较，TLR-4在“两次打击”致ALI中的作用明显增强。Objective To compare the roles of Toll-like receptor-4 （TLR-4） in the acute lung injury （ALl） induced by lipopolysaccharide （LPS） and by hemorrhagic shock and resuscitation （HSR） and LPS （＂two- hit＂） in mice. Methods Two types of mice were used in this study： free wild type mice （C3H/HeN） and TLR- 4 gene mutation type （C3H/HeJ）. Each type of mice was randomly divided into 2 groups （ n = 18） ： group sham operation ＋ LPS （group S/LPS） and group HSR ＋ LPS （group I-ISR/LPS）. Hemorrhagic shock was induced by blood withdrawal until MAP was reduced to 35-45 mm Hg and maintained for 60 min （＂first hit＂）. The animals were then resuscitated by infusion of shed blood and lactated Ringer＇ s solution, LPS 30 ttg/kg was instilled into trachea at 24 h after HSR （＂ second hit＂）. Arterial blood gas analysis was performed and the animals were then sacrificed by exsanguination at 0, 3 and 6 h after LPS（T1 ,T2 ,T3 ） . The lungs were removed. W/D lung weight ratio and MPO activity, IL-6 and IL-10 contents in the lung tissue were determined. The changing rate of the abovementioned variables at T2 ,T3 based on the values at T1 were calculated. Results In C3H/HeN animals the changing rate of PaO2 was significantly lower while the changing rate of W/D ratio, MPO activity and IL-6, IL-10 contents in the lung tissue were significantly higher in HSR/LPS group than in S/LPS group at T2,3 . But in C3H/HeJ animals the above-mentioned variables were changed at T2. Conclusion The role of TLR-4 in the ＂two-hit＂-induced ALI is stronger than that in the LPS-induced ALI in mice.

关 键 词：TOLL样受体4 呼吸窘迫综合征 成人 内毒素血症 休克 出血性 

分 类 号：R285.5[医药卫生—中药学]