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目的探讨川芎嗪(Lig)在失血性休克合并内毒素诱发急性肺损伤时对肺泡巨噬细胞(PAM)核因子(NF)-κB活化的调节干预作用。方法采用家兔失血性休克合并内毒素诱发肺损伤时模型,30只家兔随机分为:模型组、川芎嗪干预组和对照组。测动脉血气、肺湿/干质量比(W/D),提取PAM中核蛋白并用凝胶电泳迁移率(EMSA)法测NF-κB活性,原位杂交法(ISH)结合原位定量检测PAM中IKK-β的mRNA表达,并用酶联免疫吸附试验(ELSA)测PAM培养上清液中TNF-α含量。结果干预组W/D、PaCO2低于模型组,而PaO2高于模型组;模型组和干预组的IKK-βmRNA的表达、NF-κB活性、TNF-α含量均高于对照组(Ρ<0·01),干预组与模型组比较有差异(Ρ<0·05)。讨论川芎嗪可减轻失血性休克并内毒素诱发的急性肺损伤,可能与川芎嗪干预抑制肺泡巨噬细胞NF-κB的活化有关。
Objective To investigate the regulation of Ligustrazine (Lig) on the activation of nuclear factor (NF)-κB in alveolar macrophages (PAM) during hemorrhagic shock combined with endotoxin-induced acute lung injury. Methods The model of rabbit lung injury induced by hemorrhagic shock combined with endotoxin was induced. 30 rabbits were randomly divided into model group, tetramethylpyrazine intervention group and control group. Arterial blood gas, lung wet/dry mass ratio (W/D), nuclear protein extracted from PAM and NF-κB activity measured by electrophoretic mobility shift assay (EMSA), in situ hybridization (ISH) combined with in situ quantitative detection of PAM The mRNA expression of IKK-β was measured and the content of TNF-α in the PAM culture supernatant was measured by enzyme-linked immunosorbent assay (ELSA). Results W/D and PaCO2 in the intervention group were lower than those in the model group, but PaO2 was higher than that in the model group. Expressions of IKK-βmRNA, NF-κB activity and TNF-α in the model group and the intervention group were higher than those in the control group (Ρ<0 ·01) There was a difference between the intervention group and the model group (Ρ<0.05). Discussion Chuanxiongqin can reduce hemorrhagic shock and endotoxin-induced acute lung injury, and may be related to the inhibition of the activation of NF-κB in alveolar macrophages by intervention of tetramethylpyrazine.