乌司他丁对脓毒症性急性呼吸窘迫综合征大鼠晚期糖基化终末产物受体表达水平的影响  

Effect of ulinastatin on receptor of advanced glycation end products in rats with acute respiratory distress syndrome induced by sepsis

作　　者：王敏华 李文放[2] 王胜云[2] 何超[2] 刘军英[2] 

机构地区：[1]上海市浦东新区光明中医院普通外科,上海201399 [2]上海长征医院急救科

出　　处：《上海医学》2015年第4期305-309,I0001,共6页Shanghai Medical Journal

基　　金：国家自然科学基金(81171844);上海市申康医院发展中心适宜技术(SHDC12012217);上海市科学技术委员会(14495810400)资助项目

摘　　要：目的建立盲肠结扎穿孔(CLP)致大鼠脓毒症性急性呼吸窘迫综合征(ARDS)模型,观察静脉注射乌司他丁(UTI)前后大鼠血浆和支气管肺泡灌洗液(BALF)中晚期糖基化终末产物受体(RAGE)水平的变化,探讨RAGE对脓毒症性ARDS发病机制的影响,以及有效的干预措施。方法将72只Sprague-Dawley大鼠按随机数字法分入假手术组(Sham组)、CLP组、UTI组,每组24只。Sham组大鼠麻醉后只行开关腹,不行CLP,术毕腹壁皮下不注射0.9%氯化钠溶液。CLP组和UTI组大鼠均行CLP制造脓毒症性ARDS模型。造模成功后30min,Sham组和CLP组大鼠通过尾静脉注射0.9%氯化钠溶液2 mL,UTI组大鼠通过尾静脉注射UTI10万U/kg加0.9%氯化钠溶液至2mL,均为每12h重复1次。各组大鼠分别于造模后6、12、24和48h,检测血浆和BALF中RAGE水平、肺组织中RAGE mRNA相对表达量,以及肺组织病理改变。结果 CLP组在造模后6、12、24和48h各时间点的血浆和BALF中RAGE表达水平,以及肺组织中RAGE mRNA的相对表达量均显著高于Sham组和UTI组同时间点(P值均<0.05),且CLP组大鼠血浆中RAGE水平在造模后48h达高峰,BALF中RAGE水平和肺组织中RAGE mRNA相对表达量均在造模后24h达高峰(P值均<0.05);UTI组在造模后6、12、24和48h各时间点的BALF中RAGE水平,以及在造模后48h肺组织中RAGE mRNA相对表达量均显著高于Sham组同时间点(P值均<0.05),但在造模后6和48h的血浆中RAGE水平均显著低于Sham组同时间点(P值均<0.05),且UTI组大鼠血浆中的RAGE水平在造模后12h达高峰,而BALF中的RAGE水平和肺组织中RAGE mRNA相对表达量均在造模后24h达高峰(P值均<0.05)。CLP组在造模后6h的肺组织Smith评分显著高于Sham组同时间点(P<0.05),在造模后12、24、48h的肺组织Smith评分均显著高于Sham组和UTI组同时间点(P值均<0.05);UTI组在造模后6、12、24和48h的肺组织Smith评分均显著高于Sham组同时间点(P值均<0.05)。CLP组在造模后6、12、24和48h�Objective To observe the effect of ulinastatin on receptor of advanced glycation end products （RAGE） in rats with sepsis-induced acute respiratory distress syndrome （ARDS） by cecal ligation and puncture （CLP） so as to explore the mechanism of ARDS and effective intervention on it. Methods Seventy-two Sprague- Dawley rats were randomly divided into Sham operation group, CLP group and ulinastatin group. There were 24 rats in each group. The abdominal cavity of the rats in sham operation group was switched after anesthesia and no 0.9% sodium chloride solution was injected after operation. The animal models with sepsis-induced ARDS were established by CLP in CLP group and ulinastatin group. Thirty minutes after modeling, 2 mL 0.9% sodium chloride solution was given every 12 h through caudal vein in CLP group and sham operation group; ulinastatin （1×10^5 U/kg） diluted with 0.9% sodium chloride solution to 2 mL was given every 12 h through caudal vein in ulinastatin group. The concentrations of RAGE in serum and bronchoalveolar lavage fluid （BALF）, RAGE mRNA level in lung tissue, and pathological change of the lung were detected at 6, 12, 24 and 48 h after modeling. Results The concentrations of RAGE in serum and BALF and the mRNA level of RAGE in lung tissue in CLP group were significantly higher than those in sham operation group and ulinastatin group at 6, 12, 24 and 48 h after modeling （all P〈0.05）. In CLP group, serum RAGE reached the peak at 48 h after modeling, and RAGE in BALF and mRNA level of RAGE in lung tissue reached the peak at 24 h after modeling （all P〈0.05）. Compared with those in sham operation group at the same time points, RAGE in BALF at 6, 12, 24 and 48 h after modeling and mRNA level of RAGE in lung tissue at 48 h after modeling were significantly increased, while RAGE in serum at 6 and 48 h after modeling were significantly decreased （all P〈0.05）. In ulinastatin group, serum RAGE reached the peak at 12 h after modeling, and RAGE in BALF and mRNA level of RA

关 键 词：脓毒症 急性呼吸窘迫综合征 晚期糖基化终末产物受体 乌司他丁 

分 类 号：R459.7[医药卫生—急诊医学]