芍药苷减轻小鼠LPS性急性肺损伤的作用机制研究

摘要

目的:观察芍药苷(Pae)对LPS诱导的小鼠急性肺损伤的影响及其作用机制.方法:雄性BALB/c小鼠随机分为对照组、脂多糖组(LPS)、芍药苷防治组(Pae+LPS)和芍药苷对照组(Pae),予以双蒸水或Pae(20 mg/kg)灌胃,1次/d,连续3 d,于实验第3 d灌胃后1 h,腹腔注射生理盐水或LPS (20 mg/kg).观察各组小鼠肺组织形态学改变并进行肺损伤评分;用Western blotting检测肺组织髓过氧化物酶(MPO)、胞浆型磷脂酶A2(cPLA2)及磷酸化cPLA2的含量.结果:小鼠腹腔注射LPS后12 h,肺组织损伤明显,肺泡间隔增厚,大量炎症细胞浸润,可见明显肺出血及肺水肿;肺组织MPO含量、磷酸化cPLA2水平显著升高.芍药苷防治组与LPS组相比,肺组织损伤明显减轻,炎症细胞浸润减少,肺出血、肺水肿显著减轻;肺MPO含量、磷酸化cPLA2水平明显降低.芍药苷对照组与正常对照组相比,小鼠肺组织结构,MPO含量及磷酸化cPLA2水平未见明显差别.结论:芍药苷通过抑制肺组织中性粒细胞浸润、降低MPO含量和cPLA2活性,减轻小鼠内毒素性肺损伤.%AIM: To investigate the mechanisms by which paeoniflorin ( Pae ) attenuates lipopolysaccharide ( LPS ) - induced acute lung injury in mice. METHODS: Male BALB/c mice were randomly divided into 4 groups: control , LPS, Pae + LPS, and Pae. Mice were administered intragastrically with double distilled water or Pae ( 20 mg/kg ) once a day for 3 days. One hour after intragastrical treatment on the third day, LPS ( 20 mg/kg ) or normal saline was injected intraperitoneally. Twelve hours after LPS challenge, the histological changes of the lung were observed, and histology score was also assessed. The myeloperoxidase ( MPO ), cytosolic phospholipase A2( cPLA2 ) and phosphorylated cytosolic phos-pholipase A2( phospho - cPLA2) in lung tissues were detected by Western blotting. RESULTS: LPS challenge resulted in acute lung injury, activated cPLA2 and increased MPO content in lung. Pretreatment with paeoniflorin significantly attenuated lung injury induced by intraperitoneal injection of LPS. The levels of MPO and phospho - cPLA2 in the lung tissues of the mice in Pae + LPS group were lower than those in LPS group ( P < 0.05 ). CONCLUSION: Pretreatment with paeoniflorin remarkably reduces LPS - induced acute lung injury through inhibiting phosphorylation of cPLAj and decreasing neu-trophil infiltration in the lung. These findings provide a new strategy for the prevention and treatment of IPS - induced a-cute lung injury.