盐酸戊乙奎醚通过抑制FAS/FASL信号通路对创伤/失血性休克大鼠急性肺损伤肺保护作用机制的研究

    Mechanism of lung-protective effect of pentylenetetrazol hydrochloride on acute lung injury in trauma/haemorrhagic shock rats by inhibition of the FAS/FASL signaling pathway

    • 摘要:
      目的 探讨细胞凋亡与创伤失血性休克所致肺损伤关系以及盐酸戊乙奎醚是否能够通过抑制FAS/FASL信号通路减轻创伤/失血性休克所致的急性肺损伤。
      方法 制作钝性胸部创伤失血性休克模型,采用动脉血气分析、肺干湿比、采用ELISA、HE染色、Tunel染色、免疫组织化学、Western blotting等方法检测血清、肺泡灌洗液、肺组织中TNF–α、IL–1β含量,以及肺组织匀浆中FAS、FASL的表达情况。
      结果 PHC预处理和后处理组的肺干湿比明显高于模型组(P < 0.01),低于假手术组(P < 0.01),后处理组高于PHC预处理组(P < 0.01);PHC预处理组和PHC后处理组血清TNF–α、IL–1β含量、肺泡灌洗液TNF–α、肺组织中FAS、FASL和TNF–α量、Tunel染色凋亡量、肺损伤、Western blotting检测FAS、FASL表达量明显低于模型组(P < 0.01)、高于假手术组(P < 0.01);且PHC预处理低于PHC后处理组(P < 0.01)。
      结论 创伤失血性休克后FAS/FASL表达明显上调;PHC可能是通过抑制FAS/FASL信号通路表达、减轻细胞凋亡,从而减轻T/HS所致急性肺损伤。

       

      Abstract: Objective: To explore the relationship between apoptosis and trauma-hemorrhagic shock-induced lung injury and whether pentylenetetrazol hydrochloride (PHC) can attenuate trauma/hemorrhagic shock-induced acute lung injury by inhibiting the FAS/FASL signaling pathway.
      Methods A hemorrhagic shock model due to blunt chest trauma was made. Arterial blood gas analysis, lung dry-to-wet ratio were performed. TNF-α and IL-1β content in serum, bronchoalveolar lavage fluid, and lung tissues, as well as the expression of FAS and FASL in the homogenate of lung tissues were detected using ELISA, HE staining, Tunel staining, immunohistochemistry, and Western blotting.
      Results The lung dry-to-wet ratio in PHC pretreatment and post-treatment groups was significantly higher than that in the model group (P < 0.01) and lower than that in the sham-operated group (P < 0.01), and the ratio in the post-treatment group was higher than that in the PHC pretreatment group (P < 0.01). The serum levels of TNF-α and IL-1β, bronchoalveolar lavage TNF-α levels, the amount of FAS, FASL, and TNF-α in lung tissue, the amount of apoptosis by Tunel staining, and the degree of lung injury, and. the expression of FAS and FASL detected by Western blotting were significantly lower than those of the model group (P < 0.01) and higher than those of the sham-operated group; and those measures of the PHC pretreatment were lower than those of the PHC post-treatment group,
      Conclusions : FAS/FASL expression is significantly upregulated after trauma/hemorrhagic shock. PHC may attenuate trauma/hemorrhagic shock-induced acute lung injury by inhibiting the expression of the FAS/FASL signaling pathway and attenuating apoptosis.

       

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