己酮可可碱对大鼠脓毒症急性肺损伤p38MAPK活性的影响

Effect of Pentoxifylline on the Activation of p38 Mitogen Activated Protein Kinase in Rats with Septic Acute Lung Injury

关键词:  脓毒症  急性肺损伤  己酮可可碱  p38MAPK

Key words:  sepsis  acute lung injury  pentoxifylline  p38MAPK

摘要:

目的　探讨己酮可可碱(pentoxifylline，PTX)对腹腔感染致脓毒症急性肺损伤发挥肺保护作用与p38MAPK活化的关系。方法　采用盲肠结扎穿孔致脓毒症模型，将大鼠随机分为Ⅰ组(Sham组)、Ⅱ组(脓毒症CLP组)、Ⅲ组(脓毒症加西黄著胶CLP+V组)、Ⅳ组(脓毒症加生理盐水CLP+N组)、Ⅴ组(脓毒症加SB203580 CLP+SB组)、Ⅵ组(脓毒症加己酮可可碱CLP+PTX组)，其中Ⅲ组、Ⅳ组为溶媒对照组。用Western Blot检测假手术组，脓毒症1，3，6，12，24 h后p38MAPK的磷酸化，然后选择1，6，24 h分别检测应用SB203580或PTX后p38MAPK的表达，同时检测血浆TNF-α、IL-6的含量并观察24 h内肺组织病理改变。结果　与假手术组比较，脓毒症组在各个时间点p38MAPK均有较强的表达，SB203580或PTX预处理后各组的p38MAPK的磷酸化明显受到抑制，且与血浆TNF-α、IL-6的含量以及肺的病理切片变化一致。结论　己酮可可碱可能是通过抑制p38MAPK的磷酸化抑制促炎因子的过度表达，发挥对脓毒症急性肺损伤的保护作用。

Abstract:

OBJECTIVE To explore the effect of pentoxifylline (PTX) on the activation of p38MAPK in rats with septic acute lung injury induced by intra-abdominal infection. METHEDS　SD rats were subjected to sepsis caused by cecal ligation and puncture(CLP), and animals were randomly divided into Ⅰgroup(sham operation group), Ⅱgroup(sepsis CLP group), Ⅲ group (sepsis+tragacanth CLP+V group), Ⅳ group (sepsis+NS CLP+N group), Ⅴ group (sepsis+SB203580 CLP+SB group), Ⅵ group (sepsis+PTX CLP+PTX group). p38MAPK phosphorylation were measured in 1, 3, 6, 12, 24 h, respectively. 1, 6, 24 h after pretreated with SB203580 or PTX, p38MAPK phosphorylation, the concentration of plasma TNF-α, IL-6, and the pulmonary histopathology were determined. RESULTS　Compared with sham operation, p38MAPK became phosphorylated and hence activated in sepsis group. Pretreated with SB203580 or PTX, p38MAPK were inhibited, consistent with the change of the concentration of plasm TNF-α, IL-6, and the pulmonary histopathology. CONCLUSION　The result suggests that PTX　may alleviate the inflammatory reaction and produce the pulmonary protection in rats polymicrobial sepsis-induced ALI by inhibiting p38MAPK activation.