己酮可可碱弱化大鼠脓毒症急性肺损伤对p38MAPK/IκBα磷酸化的影响

Effects of Pentoxifylline Attenuates Septic Acute Lung Injury Induced by Cecal Ligation and Puncture on the Phosphorylation of p38 Mitogen Activated Protein Kinase and IκBα

关键词:  脓毒症  急性肺损伤  己酮可可碱  p38MAPK  NF-κB

Key words:  sepsis  acute lung injury  pentoxifylline  p38MAPK  NF-κB

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保护作用的上游信号机制。方法 采用盲肠结扎穿孔(cecal ligation and puncture，CLP)致脓毒症模型，将大鼠随机分为假手术组、脓毒症组、脓毒症+西黄著胶组、脓毒症+生理盐水组、脓毒症+SB203580组、脓毒症+PTX组。检测假手术组、脓毒症组各时间点(1，3，6，12，24 h)p38MAPK及IκBα的磷酸化，然后选择1，6，24 h组分别检测应用SB203580或PTX后p38MAPK及IκBα的表达，同时检测血浆TNF-α、IL-6的含量并观察24 h组肺组织病理改变。结果 与假手术组比较，脓毒症组在各个时间点p38MAPK及IκBα均有较强的表达，SB203580或PTX预处理后各组的p38MAPK及IκBα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 PTX对脓毒症急性肺损伤的保护作用以及抑制促炎因子产生的作用可能是通过抑制p38MAPK的磷酸化从而抑制NF-κB的活化而产生的。

Abstract:

OBJECTIVE To investigate the upstream signal transduction mechanism of pentoxifylline(PTX) on acute lung injury (ALI) in rats sepsis induced by intra-abdominal infection. METHODS SD rats were subjected to sepsis caused by cecal ligation and puncture(CLP), animals were randomly divided into sham operation group, sepsis group, sepsis+tragacanth group, sepsis+normal saline group, sepsis+SB203580 group, sepsis+PTX group. p38MAPK and IκBα phosphorylation were measured in 1, 3, 6, 12, 24 h respectively. And 1, 6, 24 h after pretreated with SB203580 or PTX, p38MAPK and IκBα phosphorylation, the concentration of plasma TNF-α, IL-6 were examined and the pulmonary histopathology after induced 24 h were determined. RESULTS Compared with sham operation group, p38MAPK and IκBα became phosphorylated and hence activated in sepsis group. Pretreated with both p38MAPK and IκBα were inhibited, consistent with the change of the concentration of plasma TNF-α, IL-6 and the pulmonary histopathology. CONCLUSION These results suggest that the inhibitory activity of pentoxifylline on the production of proinflammatory mediators and the pulmonary protection seems to be mediated via inhibition of p38MAPK and then suppression the activation of NF-κB in polymicrobial sepsis-induced ALI.