基于MKP-1/Nrf2/NF-κB调控肺泡上皮细胞屏障结构因子途径研究CoQ10对急性肺损伤的保护作用及机制

急性肺损伤（ALI）是兽医临床中动物的一种高发病率和高死亡率呼吸性系统疾病，目前探寻防治ALI有效措施及药物是临床兽医学和医学的研究热点与难点。针对前期研究中发现辅酶Q10（CoQ10）对小鼠肺损伤具有明显的保护作用这一科学现象，课题组建立小鼠ALI模型，在研究CoQ10对氧化应激和炎性因子调控作用的同时，重点从改善肺泡上皮屏障这一新的角度，观察CoQ10对小鼠ALI的保护作用，并构建LPS诱导小鼠肺泡上皮细胞损伤模型，利用CRISPR/Cas9基因编辑技术敲除MKP-1、Nrf2、HO-1及NQO1基因，进一步探究CoQ10通过调控MKP-1/Nrf2信号通路，以Nrf2为关键位点上调E-cadherin、occludin及ZO-1表达的作用机制，为兽医和医学临床中推进CoQ10在防治ALI中的应用提供理论基础和试验依据。

Acute lung injury (ALI) is a respiratory disease with high morbidity and mortality in veterinary clinic. At present, exploring effective measures and drugs for prevention and treatment of ALI is a research hotspot and difficulty in clinical veterinary medicine and medicine. In view of the scientific phenomenon that coenzyme Q10 (CoQ10) has obvious protective effect on lung injury in mice in the previous study, the research team established mice ALI model. While studying the regulatory effect of CoQ10 on oxidative stress and inflammatory factors, the protective effect of CoQ10 on ALI in mice was observed from a new perspective of improving alveolar epithelial barrier. Meanwhile, a mice alveolar epithelial cell injury model induced by LPS was constructed. CRISPR/Cas9 gene editing technology was used to knock out MKP-1, Nrf2, HO-1 and NQO1 genes, so as to further explore the mechanism of CoQ10 up-regulating E-cadherin, occludin and ZO-1 expression by regulating MKP-1/Nrf2 signaling pathway, which provide theoretical and experimental basis for the application of CoQ10 in the prevention and treatment of ALI in veterinary and medical clinical.