OBJECTIVE: To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.
METHODS: Of 22 patients with LARS (pre- and post/5.8 ± 3.8 months after LARS) and 25 healthy controls (HCs) were included. All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy, during which esophageal biopsy samples were collected using endoscopic techniques. Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.
RESULTS: Post-LARS samples showed significant increases in proinflammatory cytokines [interleukin (IL)-1β, interferon-γ, C-X-C chemokine ligand 2 (CXCL2)], anti-inflammatory cytokines [CC chemokine ligand (CCL) 11, CCL13, CCL17, CCL26, CCL1, CCL7, CCL8, CCL24, IL-4, IL-10], and homeostatic cytokines (CCL27, CCL20, CCL19, CCL23, CCL25, CXCL12, migration inhibitory factor) compared to both HCs and pre-LARS samples. CCL17 and CCL21 levels were higher in pre-LARS than in HCs (P < 0.05). The mRNA expression levels of AKT1, fibroblast growth factor 2, HRAS, and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS. CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs (P < 0.05).
CONCLUSIONS: The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium. Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS. The anti-inflammatory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.
目的:探讨炎症生物分子在LARS中的作用,并评估食管上皮恢复所需的时间。
方法:纳入22例LARS患者(LARS前后/5.8±3.8个月)和25例健康对照(HCs)。所有受试者均接受24小时多通道腔内阻抗-pH监测和上消化道内镜检查,在此期间使用内窥镜技术收集食管活检样本。通过逆转录聚合酶链反应和多重酶联免疫吸附试验研究了食管活检中的炎症分子。
结果:LARS后样本显示促炎细胞因子[白细胞介素(IL)-1β,干扰素-γ,C-X-C趋化因子配体2(CXCL2)],抗炎细胞因子[CC趋化因子配体(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],和稳态细胞因子(CCL27,CCL20,CCL19,CCL23,CCL25,CXCL12,迁移抑制因子)与HC和前LARS样品相比。LARS前的CCL17和CCL21水平高于HC(P<0.05)。AKT1、成纤维细胞生长因子2、HRAS、丝裂原活化蛋白激酶4在LARS后与LARS前相比显着降低。与HC相比,前LARS中的CCL2和表皮生长因子基因水平显着增加(P<0.05)。
结论:LARS后促炎蛋白的存在提示上皮中正在发生炎症。稳态细胞因子水平升高表明细胞平衡在LARS后维持约6个月。LARS后的抗炎反应显示对炎性损伤的抑制和持续的术后恢复。