Abstract：
UNASSIGNED: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved.
UNASSIGNED: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2).
UNASSIGNED: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway.
UNASSIGNED: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.
UNASSIGNED: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2).
UNASSIGNED: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway.
UNASSIGNED: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.
摘要：
■认知障碍是急性呼吸窘迫综合征（ARDS）的严重并发症。新兴研究揭示了吡咯烷二硫代氨基甲酸酯（PDTC）对改善手术引起的认知障碍的作用。该研究的主要目的是研究PDTC是否可以抵抗ARDS引起的认知功能障碍，并确定相关的潜在机制。
■气管内滴注脂多糖（LPS）建立ARDS大鼠模型，然后用PDTC治疗。通过Morris水迷宫分析大鼠的认知功能,和促炎细胞因子通过定量实时PCR评估，酶联免疫吸附测定，和蛋白质印迹分析。进行双荧光素酶报告基因测定以鉴定miR-181c与其靶基因之间的关系。TAK1结合蛋白2(TAB2)。
■结果表明，在LPS诱导的ARDS模型中，PDTC改善了认知障碍并减轻了海马的神经炎症。此外，我们证明miR-181c在ARDS大鼠海马中表达下调,通过PDTC治疗恢复。体外研究表明，miR-181c通过抑制核因子（NF）-κB信号通路中的关键分子TAB2减轻LPS诱导的促炎反应。
■PDTC通过调节miR-181c/NF-κB轴介导的神经炎症改善LPS诱导的ARDS的认知障碍，提供治疗这种疾病的潜在机会。
■气管内滴注脂多糖（LPS）建立ARDS大鼠模型，然后用PDTC治疗。通过Morris水迷宫分析大鼠的认知功能,和促炎细胞因子通过定量实时PCR评估，酶联免疫吸附测定，和蛋白质印迹分析。进行双荧光素酶报告基因测定以鉴定miR-181c与其靶基因之间的关系。TAK1结合蛋白2(TAB2)。
■结果表明，在LPS诱导的ARDS模型中，PDTC改善了认知障碍并减轻了海马的神经炎症。此外，我们证明miR-181c在ARDS大鼠海马中表达下调,通过PDTC治疗恢复。体外研究表明，miR-181c通过抑制核因子（NF）-κB信号通路中的关键分子TAB2减轻LPS诱导的促炎反应。
■PDTC通过调节miR-181c/NF-κB轴介导的神经炎症改善LPS诱导的ARDS的认知障碍，提供治疗这种疾病的潜在机会。
