川芎嗪对肺损伤肺泡巨噬细胞中NF-κB活化的影响

Effects of Ligustrazini on activation of NF-κB in pulmonary alveolar macrophages(PAM) in rabbits

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 effects of Ligustrazini （Lig） on the activation of NF-κB in PAM in acute lung injury （ALl） induced by hemorrhagic shock （HS） associated with endotoxin in rabbits. Methods Thirty rabbits were randomly divided into three groups： HS plus endotoxin group （group A）, Lig treatment group （group B） and the normal control group （group C）. Arterial blood gas was measured before the animals were killed. Wet/dry ratios （W/D） of the lungs in the three groups were determined, The nuclear protein of the alveolar macrophages was extracted from bronchoalveolar lavage fluid （BALF）, and the activity of NF-κB was assayed with electrophoretic mobility shift assay （EMSA）. The expression of IKK-β mRNA in the alveolar macrophages, tumor necrosis factor-α （TNF-α） content in culture supernatant of the alveolar macrophages were assesscd by in situ hybridization （ISN） and enzyme-linked immunosorbent assay （ ELISA）, respectively. Microscopic examination of the lung was also done. Results In group B, partial pressure of carbon dioxide in artery （ PaCO2 ） and W/D were lower than those in group A, and partial pressure of arterial oxygen （ PaO2 ） was higher than those in group A. The expression level of IKK-β mRNA and activity of NF-κB, the level of TNF-α were significantly higher in group A and group B than that in group C （ P 〈 0.01 ）. IKK-β mRNA level and NF-κB activity, TNF-α level in group B were lower than in group A （ P 〈 0.05）. Conclusion Ligustrazini treatment could inhibit the expression of IKK-β and NF-κB, significantly decrease the concentration of TNF-α and alleviate the lung injury. This phenomenon may be related with effects of Ligustrazini on inhibting NF-κB activation in pulmonary alveolar macrophages.