BACKGROUND Sepsis is a systemic inflammatory response syndrome and leads to patient's death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism. MATERIAL AND METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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MEF2C 通过上调 AQP1 减轻盲肠结扎和穿刺 (CLP) 诱导的脓毒症大鼠的急性肺损伤。

背景脓毒症是一种全身性炎症反应综合征，会导致患者死亡。目的：探讨肌细胞增强因子2（MEF2C）对脓毒症急性肺损伤（ALI）的影响及其可能机制。材料与方法 建立盲肠结扎和穿刺（CLP）致脓毒症大鼠模型。肺损伤以肺湿干重比测定，炎症细胞因子的浓度，包括肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-1β和IL-10，通过以下方法测定酶联免疫吸附血清学检测试剂盒。TUNEL染色法检测细胞凋亡。结果 有趣的是，MEF2C 在该模型中被下调。此外，腺相关病毒 (AAV)-MEF2C 治疗显着抑制 TNF-α、IL-1β、和 IL-6 浓度，但促进 CLP 攻击大鼠血清中的 IL-10 浓度。此外，MEF2C 的过表达减轻了 CLP 诱导的肺损伤。有趣的是，证实 AAV-MEF2C 治疗可抑制 CLP 诱导的脓毒症大鼠的细胞凋亡，并促进水通道蛋白 APQ1 的表达。从机制上讲，救援实验表明 MEF2C 通过上调 AQP1 来减轻 CLP 诱导的肺炎症反应和细胞凋亡。结论 总之，MEF2C的过表达通过上调AQP1抑制CLP诱导的肺炎症反应和细胞凋亡，为脓毒症诱导的ALI提供了新的治疗靶点。证实 AAV-MEF2C 治疗可抑制 CLP 诱导的脓毒症大鼠的细胞凋亡并促进水通道蛋白 APQ1 的表达。从机制上讲，救援实验表明 MEF2C 通过上调 AQP1 来减轻 CLP 诱导的肺炎症反应和细胞凋亡。结论 总之，MEF2C的过表达通过上调AQP1抑制CLP诱导的肺炎症反应和细胞凋亡，为脓毒症诱导的ALI提供了新的治疗靶点。证实 AAV-MEF2C 治疗可抑制 CLP 诱导的脓毒症大鼠的细胞凋亡并促进水通道蛋白 APQ1 的表达。从机制上讲，救援实验表明 MEF2C 通过上调 AQP1 来减轻 CLP 诱导的肺炎症反应和细胞凋亡。结论 总之，MEF2C的过表达通过上调AQP1抑制CLP诱导的肺炎症反应和细胞凋亡，为脓毒症诱导的ALI提供了新的治疗靶点。