基于miR-125靶向调控A20/NLRP3信号探讨穿山龙减轻呼吸机诱导性肺损伤的机制研究

呼吸机诱导性肺损伤（VILI）是机械通气的常见并发症，其发病机制尚未完全阐明，也缺乏有效的治疗药物。A20作为机体重要的保护性蛋白，一方面能有效抑制NF-κB/NLRP3信号，减轻炎症反应；另一方面，该蛋白也受miR-125靶向调控，进而发挥抑炎作用，但这一途径是否参与调控VILI未见报道。穿山龙是临床治疗肺系疾病的常用药物，既往研究显示该药物可作用于巨噬细胞NF-κB/NLRP3信号，减轻肺部炎症。基于此，我们考虑穿山龙是改善VILI的潜在药物，并提出科学假说：穿山龙通过上调miR-125，靶向促进A20表达，进而抑制巨噬细胞NF-κB/NLRP3，减轻VILI。研究拟使用不同剂量穿山龙对体内外牵张模型进行干预，通过药物抑制剂、基因沉默及过表达等技术，揭示VILI的发病机制和穿山龙的干预靶点，为扩大穿山龙的临床应用和中医中药防治呼吸危重症开阔新思路。

Ventilator-induced lung injury (VILI) is a common complication of mechanical ventilation without completely understood mechanism and effective therapeutic approaches. As an important protective protein in body, A20 not only inhibits the NF-κb/NLRP3 signaling, but also exerts anti-inflammatory effects under the control of miR-125. However, whether miR-125 and A20/NLRP3 signaling are involved in the regulation of VILI remains unclear. Rhizoma Dioscoreae Nipponicae (RDN) is a commonly used traditional Chinese medicine in the clinical treatment. Previous studies have confirmed that RDN could effectively inhibit NF-κB/NLRP3, to alleviate the lung inflammations. Based on these, we considered it to be a promising candidate for treating VILI, thus proposes a hypothesis that RDN could upregulate the expression level of miR-125, and terget to promote A20 expression, and then alleviate the VILI via inhibiting the macrophage NF-κB/NLRP3 signaling. The study is designed to reveal the pathogenesis of VILI and the intervention target of RDN during VILI by using drug inhibitors, gene silencing and overexpression techniques in both vivo and vitro mechanical stretch model, aiming to expand the clinical application of RDN and provide new insights for the treatment of VILI using traditional Chinese medicine.