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

发布时间：2018-10-30 15:33

【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(P0.05),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各时间点肺组织中RAGE mRNA相对表达量均与肺组织Smith评分呈正相关(r=0.583、0.650、0.595、0.853,P值均0.01)。结论 CLP致脓毒症性ARDS模型动物肺组织均出现不同程度的损伤,其程度与血浆和BALF中的RAGE水平,以及肺组织中RAGE mRNA表达水平密切相关,表明RAGE途径可能参与了脓毒症性ARDS的发病过程,静脉注射UTI可能通过抑制RAGE水平减轻肺组织损伤程度。
[Abstract]:Objective to establish a model of septic acute respiratory distress syndrome (ARDS) induced by cecal ligation and perforation of (CLP) in rats. To observe the changes of advanced glycation end product receptor (RAGE) (RAGE) in plasma and bronchoalveolar lavage fluid (BALF) of rats before and after intravenous injection of ulinastatin (UTI), and to explore the effect of RAGE on the pathogenesis of septic ARDS. And effective interventions. Methods Seventy-two Sprague-Dawley rats were randomly divided into sham-operation group (Sham group,), CLP group, UTI group, 24 rats in each group). Sham rats were anesthetized only by switching abdomen, not CLP,. At the end of operation, 0.9% sodium chloride solution was not injected subcutaneously into the abdominal wall. CLP was used to make septic ARDS model in both CLP group and UTI group. 30 minutes after the model was successfully established, rats in Sham group and CLP group were injected through tail vein with 0.9% sodium chloride solution. Rats in 2 mL,UTI group were injected with UTI10 10000 U/kg and 0.9% sodium chloride solution to 2 mL through tail vein, all of them were repeated every 12 hours. The levels of RAGE in plasma and BALF, the relative expression of RAGE mRNA in lung tissue, and the pathological changes of lung tissue were detected in each group at 6: 12 and 48 hours after modeling. Results the levels of RAGE expression in plasma and BALF and the relative expression of RAGE mRNA in lung tissue in CLP group were significantly higher than those in Sham group and UTI group at 24 and 48 hours after modeling (P < 0. 05). In CLP group, the plasma RAGE level reached its peak at 48h after modeling, and the RAGE level in BALF and the relative expression of RAGE mRNA in lung tissue reached its peak at 24 h after modeling (P < 0. 05). The levels of RAGE in BALF and the relative expression of RAGE mRNA in lung tissue in UTI group were significantly higher than those in Sham group at 24 and 48 hours after model making (P < 0. 05). However, the levels of RAGE in plasma at 6 and 48 hours after modeling were significantly lower than those in Sham group at the same time point (P < 0. 05), and the plasma RAGE level in UTI group reached its peak at 12 h after modeling. However, the level of RAGE in BALF and the relative expression of RAGE mRNA in lung tissue reached the peak at 24 hours after modeling (P < 0. 05). The Smith score of lung tissue in the group of 0. 05). CLP was significantly higher than that in the group of Sham at the same time point (P0.05). The Smith scores of lung tissue were significantly higher than those of Sham group and UTI group at the same time point (P < 0. 05). The Smith score of lung tissue in UTI group was significantly higher than that in Sham group at 24 and 48 hours after model making (P < 0. 05). The relative expression of RAGE mRNA in lung tissue of UTI group was significantly higher than that in Sham group at each time point of 6: 1212 and 48 hours after model making. The relative expression of RAGE mRNA in lung tissue was positively correlated with Smith score of lung tissue. The correlation was (r = 0.583) ~ (0.650) ~ (0.595N) ~ (0.853), P = 0.01). Conclusion the lung tissues of septic ARDS model rats induced by CLP have different degree of injury, which is closely related to the level of RAGE in plasma and BALF, and the expression of RAGE mRNA in lung tissue. The results suggest that RAGE pathway may be involved in the pathogenesis of septic ARDS, and intravenous UTI may reduce lung tissue injury by inhibiting RAGE level.
【作者单位】：上海市浦东新区光明中医院普通外科;上海长征医院急救科;
【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
【分类号】：R459.7

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