普通肝素通过降低肺组织Rho激酶活性缓解脓毒症小鼠的肺损伤

目的探讨普通肝素对腹腔注射脂多糖(LPS)所致脓毒症小鼠肺组织Rho激酶活性以及肺损伤的影响。方法腹腔注射LPS制作小鼠脓毒症模型,将小鼠随机分为对照组、LPS组和LPS+肝素治疗组。分别于造模后3h和6h收集血液标本和肺组织。ELISA法分别测定血清TNF-α、IL-1β浓度;取肺组织进行HE染色,测定肺水含量;用Westernblot法观察肺组织中p-MYPT1蛋白表达变化。结果 LPS组和肝素治疗组3h和6h的血浆TNF-α和IL-1β含量均显著高于正常对照组(P<0.05);与LPS组比较,肝素组3h和6h的血浆TNF-α和IL-1β含量均有显著降低(P<0.05);肝素可以缓解脓毒症小鼠肺损伤程度(6h),降低肺水含量(6h),下调肺组织p-MYPT1蛋白表达(3h,6h)。结论普通肝素缓解脓毒症小鼠的肺损伤可能与降低肺组织Rho激酶活性相关。

Unfractionated heparin attenuates acute lung injury in a mouse model of sepsis by inhibiting Rho kinase activity

Objective To investigate whether heparin has a beneficial effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to further explore the possible underlying mechanism. Methods C57BL/6J mice were randomly divided into three groups: control and LPS(intraperitoneal injection of a high dose of LPS) and LPS+heparin groups. Blood was collected and TNF-α and IL-1β levels in plasma was determined by ELISA; lungs were harvested, pathology and lung water content were examined, the level of phosphorylated-MYPT1 protein in lungs was measured by Western blot 3h and 6h after injection of LPS. Results The increased TNF-α and IL-1β levels in plasma by LPS could be significantly inhibited by pretreatment of heparin, heparin pretreatment also inhibited LPS-induced pathological changes in the lungs and LPS-induced increase of lung water content and downregulated the levels of phosphorylated-MYPT1 protein in lung tissue. Conclusion The inhibition of heparin on the lung injury induced by LPS might be related to the downregulation of Rho kinase activity.