PDF(Pubmed)
Abstract：
BACKGROUND: Currently, the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors, but they are not a cure, and some patients don\'t respond well or refuse long-term use. Therefore, alternative therapies are needed to understand the disease and develop better treatments. Laparoscopic anti-reflux surgery (LARS) can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects. Successful LARS improves typical gastroesophageal reflux symptoms in most patients, mainly by reducing the exposure time to gastric contents in the esophagus. Amelioration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.
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.
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.
摘要：
背景：目前，胃食管反流的主要治疗方法是质子泵抑制剂抑酸，但它们不是一种治疗方法，有些患者反应不佳或拒绝长期使用。因此,需要替代疗法来了解疾病并开发更好的治疗方法。腹腔镜抗反流手术（LARS）可以解决这些患者的症状，并在预防有害影响后评估食管愈合中起重要作用。成功的LARS改善了大多数患者的典型胃食管反流症状，主要是通过减少食道胃内容物的暴露时间。在有害攻击停止后，有望改善食管上皮中的炎症反应和恢复反应。
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。
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。
