Department of Critical Care Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.
Department of Critical Care Medicine, Zhongshan Torch Development Zone Hospital, Zhongshan, Guangdong 528437, China.
Allergol Immunopathol (Madr). 2021 Sep 1;49(5):117-124. doi: 10.15586/aei.v49i5.477. eCollection 2021.
Sepsis is a systemic inflammatory response syndrome and leads to patient's death. To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.
The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet-dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.
Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expression. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.
In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.
败血症是一种全身炎症反应综合征，可导致患者死亡。本研究旨在探讨肌细胞增强因子 2（MEF2C）对败血症相关性急性肺损伤（ALI）的影响及其可能的机制。
建立盲肠结扎穿孔（CLP）诱导的败血症大鼠模型。通过肺湿/干重比来评估肺损伤，通过酶联免疫吸附试验试剂盒来检测炎症细胞因子（TNF-α、IL-6、IL-1β 和 IL-10）的浓度。通过 TUNEL 染色法检测细胞凋亡。
有趣的是，在该模型中 MEF2C 表达下调。此外，AAV-MEF2C 治疗显著抑制 CLP challenged 大鼠血清中 TNF-α、IL-1β 和 IL-6 的浓度，同时促进 IL-10 的浓度。此外，过表达 MEF2C 可减轻 CLP 诱导的肺损伤。有趣的是，AAV-MEF2C 治疗可抑制 CLP 诱导的败血症大鼠的细胞凋亡，同时促进水通道蛋白 APQ1 的表达。机制研究表明，MEF2C 通过上调 AQP1 减轻 CLP 诱导的肺炎症反应和细胞凋亡。
综上所述，过表达 MEF2C 通过上调 AQP1 抑制 CLP 诱导的肺炎症反应和细胞凋亡，为败血症相关性 ALI 提供了一种新的治疗靶点。
