HMGB1在a2A-肾上腺素受体介导脓毒血症大鼠急性肺损伤的作用

Effect of High Mobility Group Box-1 Protein on α2A-Adrenoceptors-Mediated Acute Lung Injury in a Rat Model of Sepsis

目的:探讨HMGB1在a2A-肾上腺素受体介导脓毒血症大鼠急性肺损伤(ALI)的作用。方法:64大鼠建立盲肠结扎穿孔法(CLP)脓毒症模型,随机均分为以下两组:CLP组及CLP+马来酸钠组。各组分别于模型建立后2(T1)、6(T2)、12(T3)、24 h(T4)时检测大鼠血清TNF-、高迁移率族蛋白1(HMGB1)及IL-10含量。CLP24 h后检测肺组织干湿重比(W/D)和髓过氧化物酶活性(MPO)及HMGB1表达;并采用HE法进行肺组织学评分。结果:CLP+马来酸钠组T2时的TNF-水平明显低于CLP组(P<0.05);而HMGB1在T2、T3及T4均明显低于CLP组(P<0.05);IL-10在各个时间点比较结果差异无统计学意义(P>0.05)。CLP+马来酸钠组肺组织W/D、MPO活性、肺组织损伤评分均明显低于CLP组(P<0.05)。CLP+马来酸钠组肺组织HMGB1表达明显低于CLP组(P<0.05)。结论:HMGB1参与了ALI的病理过程,a2A-肾上腺素受体阻断可以通过抑制HMGB1从而改善ALI时的肺功能。

Objective： To investigate the effect of high mobility group box-1 protein on α2A-adrenaline receptors-mediated acute lung injury in a rat model of sepsis.Methods： In a sepsis model by cecal ligation and puncture（CLP）,sixty-four SD rats were randomly divided into the following groups： CLP group and CLP ＋ maleate group.Plasma levels of TNF-α,HMGB1 and IL-10 were determined at the following time points： 2（T1）,6（T2）,12（T3） and 24 h（T4） after CLP.Lung was removed for the determinations of pulmonary wet-to-dry ratio（W/D）,myeloperoxidase activity（MPO）,total histological scores and HMGB1 immunohistochemistry analysis 24 h after CLP.Results： Plasma levels of TNF-α at T2 and HMGB1 at T2,T3 and T4 were significantly lower in CLP ＋ maleate group than CLP group（P〈0.05）.There was no difference in IL-10 over time between groups（P〉0.05）.Pulmonary levels of W/D,MPO,total histological scores and HMGB1 expression were significantly lower than those in CLP group（P〈0.05）.Conclusions： HMGB1 plays a key role in the pathophysiology of ALI,and antagonism of α2A-adrenoceptors improves pulmonary function by inhibiting HMGB1.