PA-MSHA对脓毒症大鼠的肺组织炎症反应的影响

摘要

Objective:To investigate the effects and the possible mechanism of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin(PA-MSHA) on the septic serum-induced inflammatory response in lung tissues of rats.Methods:120 Sprague-Dawley( SD) rats of healthy grade were randomized into sham operation group (SC group,n=30),sepsis group (CLP group,n =30),PA-MSHA treatment before CLP (PreT group,n =30),and PA-MSHA treatment after CLP (PosT group,n=30) by random digit tables.Murine septic models were established through cecal ligation puncture (CLP).Rats in each group were sacrificed at 12,24 and 36 h after operation,and blood was collected to determine the serum TNF-α,IL-6,IL-10 and TGF-βconcentra-tion.Lung tissue samples were also obtained to determine the expression of TLR4 mRNA by real-time PCR.Pathological changes in lung tissues were ob-served with light microscopy after HE staining,and flow cytometry was used to examine the changes of TLR4 expression in peripheral blood monocytes. Results:Serum TNF-a and IL-6 concentration in PreT group were significantly lower ,yet IL1-0 and TGF-βconcentration were significantly higher as com -pared with that of CLP and PosT groups (P<0.01).Expression of TLR4 mRNA was markedly decreased(P <0.05),and the pulmonary pathological scores were better than the other two groups (P<0.01).Conclusion:Preoperative administration of PA-MSHA can significantly reduce the inflammatory reaction and pathological injury of the lungs in septic rats.%目的：探讨铜绿假单胞菌甘露糖敏感血凝素（ PA-MSHA ）对脓毒症致急性肺损伤炎症反应的影响及可能机制。方法：健康SD大鼠120只按随机数字法分为假手术对照组（SC组，n＝30）、脓毒症组（CLP组，n＝30）、术前治疗组（PreT组，n＝30）和术后治疗组（PosT组，n＝30）。以盲肠结扎穿孔法（CLP）复制大鼠脓毒症模型。制模后12、24、36 h分别采集外周血测定血清细胞因子（TNF-α、IL-6、IL-10和TGF-β）并处死动物，实时RT-PCR方法检测各组肺组织Toll样受体4（TLR4）mRNA表达；计算肺损伤病理评分；采用流式细胞术检测大鼠外周血单核细胞TLR4阳性率。结果：脓毒症大鼠中PreT组与CLP组和PosT组相比，PreT组血清细胞因子TNF-α、IL-6浓度降低而细胞因子IL1-0、TGF-β浓度均高于CLP组和PosT组（ P＜0．01）。脓毒症大鼠中PreT组外周血单核细胞TLR4阳性率和肺组织TLR4 mRNA表达水平低于CLP组和PosT组（P＜0．05），肺组织病理学评分也优于另两组（P＜0．01）。结论：术前给予PA-MSHA 可以明显下调脓毒症大鼠的炎症反应，从而减轻肺病理损伤程度。