脂质微泡介导转染MIF siRNA对小鼠急性肺损伤的保护作用

目的：通过探讨超声微泡基因转染系统转染MIF siRNA对小鼠急性肺损伤的保护作用,评价超声微泡基因转染系统的有效性。方法：以脂多糖（LPS）诱导小鼠建立急性肺损伤动物模型,随机分成4组：正常对照组（Con）、LPS刺激组（LPS）、LPS＋PC＋MIF siRNA治疗组（PC＋MIF siRNA）、LPS＋WP＋MIF siRNA治疗组（WP＋MIF siRNA）;通过超声微泡基因转染系统转染MIF siRNA,运用EMSA、Western-Blot、ELISA和相关病理检测技术,观察小鼠肺组织NF-κB/IκB-α表达、炎症介质TNF-α、IL-1β、IL-6水平,及肺组织湿干重比和炎症病理病变,探讨MIF siRNA对小鼠急性肺损伤的保护作用。结果：WP＋MIF siRNA治疗组通过上调肺组织细胞浆中IκB-α表达,对LPS刺激激活的细胞核NF-κB有明显抑制作用、从而抑制炎症介质TNF-α、IL-1β、IL-6释放,减轻小鼠肺组织病理损伤。但PC＋MIF siRNA治疗组对LPS刺激导致的小鼠肺损伤无任何改善的治疗作用。结论：脂质微泡/PEI-Chol介导的基因转染系统能有效转染MIF siRNA,对LPS介导的小鼠急性肺损伤具有一定的保护作用。

Protective effect of MIF siRNA mediated by lipid microbubbles on acute lung injury in mice

AIM：To investigate the protective effect of MIF siRNA mediated by ultrasound lipid microbubbles gene transfer system and evaluate the efficacy of this gene transfer system. METHODS： The model of acute lung injury was induced by LPS in mice which were randomly divided into 4 groups： normal control group （Con）, LPS stimulation （LPS）, LPS ＋ PC ＋ MIF siRNA treatment group （PC ＋ MIF siRNA）, LPS ＋ WP ＋ MIF siRNA treatment group （WP ＋ MIF siRNA）. The MIF siRNA was transfected by microbubbles ultrasound. These methods including EMSA, Western-Blot, ELISA and HE stained for histopathological examination were used to observe the expressions of NF-κB and IκB-α, to detect the levels of inflammatory mediators of TNF-α, IL-1β, IL-6, and to assess the pathological changes. RESULTS：MIF siRNA was carried and transferred by WP ＋ MIF siRNA which up-regulated the expression of IκB-α in cytoplasm and significantly inhibited the expression of NF-κB in nucleus, then inhibited the levels of inflammatory mediators of TNF-α, IL-1β, IL -6 and improved the pathological changes. But the PC＋ MIF siRNA treatment group has no any improvement on acute lung injury in mice. CONCLUSION： MIF siRNA can be effectively transferred by lipid microbubbles gene transfer system and have protective effect on acute lung injury in mice.