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中国临床研究:2019,32(9):1175-1180
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8-羟基脱氧鸟苷在胃食管反流病合并房颤患者食管组织中的表达及作用
(1.新疆医科大学,新疆 乌鲁木齐 830054;2.新疆维吾尔自治区人民医院心外科,新疆 乌鲁木齐 830001;3.新疆维吾尔自治区人民医院普外微创研究所,新疆 乌鲁木齐 830001;4.新疆维吾尔自治区人民医院微创、疝和腹壁外科,新疆 乌鲁木齐 830001)
Expression and role of 8-OHdG in esophageal tissues of patients with gastroesophageal reflux disease complicated with atrial fibrillation
摘要
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投稿时间:2018-12-27   网络发布日期:2019-09-20
中文摘要: 目的探讨8-羟基脱氧鸟苷(8-OHdG)以及炎症因子在胃食管反流病(GERD)合并心房颤动(AF)患者食管黏膜中的表达及其在AF发生中的意义。方法按照纳入、排除标准选取2017年1月至2018年11月间在新疆维吾尔自治区人民医院收治的90例患者设为研究组。同期完成体检的23例健康受试者设为对照组。研究组均行24 h动态心电图、24 h pH值监测、高分辨率食管测压监测并内镜下取食管齿状线上3 cm 处的局部黏膜作为标本,后续采用HE染色、免疫组化、RT-PCR、ELISA等方法分析组织炎症程度、氧化损伤标记物8-OHdG及炎症因子[单核细胞趋化蛋白1(MCP-1)、白细胞介素(IL)-8、肿瘤坏死因子(TNF)-α]的表达及血清浓度。结果根据患者的临床表现,内镜及24 h动态心电图检查,将其分为GERD合并AF组(AF组)、GERD不合并AF组(非AF组)和对照组。食管24 h pH监测比较显示,AF组弱酸反流(40.05)。光镜下观察发现,对照组黏膜组织形态基本完整,未见水肿或中性粒细胞等免疫细胞的浸润;非AF组可见中度中性粒细胞的浸润和炎症反应;而AF组食管黏膜组织出现不同程度的中性粒细胞,嗜酸性粒细胞等免疫细胞的浸润、乳头延长、水肿等炎症性改变。AF组炎症评分达到高峰,并显著高于非AF组(P<0.01)。免疫组化结果发现,对照组8-OHdG主要表达在食管上皮层、黏膜及黏膜下层,而AF组8-OHdG的表达几乎覆盖全层黏膜,表示严重的组织氧化损伤。RT-PCR和ELISA实验发现,与对照组相比,8-OHdG、MCP-1、IL-8、TNF-α的mRNA相对表达量以及其血清浓度,在非AF组和AF组中明显上升,且AF组中达到高峰,三组之间差异具有统计学意义(P<0.01)。Pearson相关性分析得出,AF组中8-OHdG血清浓度分别与Demeester评分及MCP-1、IL-8、TNF-α血清浓度之间具有正相关关系(P<0.01)。结论8-OHdG以及炎症因子(MCP-1、IL-8、TNF-α)在GERD合并AF患者食管黏膜的表达及血清浓度显著增高,可能与酸反流诱发AF的产生密切相关。
Abstract:Objective To investigate the expression of 8-hydroxy-2′ deoxyguanosine (8-OHdG) and inflammatory cytokines in esophageal mucosa of patients with gastroesophageal reflux disease (GERD) complicated with atrial fibrillation (AF) and their significance in the development of AF. Methods According to the inclusion and exclusion criteria,67 patients with GERD hospitalized in Xinjiang Uygur Autonomous Region People′s Hospital from January 2017 to November 2018 were selected as research group,and 23 healthy subjects were served as control group at the same time.All patients were given 24-hour dynamic electrocardiogram,24-hour pH monitoring,high-resolution esophageal manometry(HRM)monitoring,meanwhile endoscopy was performed to take the local mucosa at 3 cm of the dentate line of the esophagus as specimens.Using HE staining,immunohistochemistry,RT-PCR and ELISA,the degree of tissue inflammation,the expressions of 8-OHdG and inflammatory factors [monocyte chemoattractant protein-1(MCP-1),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α)] and their concentrations in blood were analyzed. Results Based on the clinical examinations,the patients in research group were subdivided into AF group (GERD combined with AF) and non-AF group (GERD without AF).24 h pH monitoring showed that the numbers of weak acid reflux (4P<0.05).There were no significant differences in HRM monitoring among three groups (all P>0.05).Light microscopy showed that the mucosa was basically intact without edema or neutrophil infiltration in control group;moderate neutrophil infiltration and inflammatory reaction were observed in non-AF group;inflammatory pathological changes of infiltration of neutrophils,eosinophils and other immune cells in different degrees,prolongation of papillae and edema were observed in AF group.The inflammatory score in AF group was significantly higher than that in non-AF group (P<0.01).Immunohistochemistry showed that 8-OHdG expression in control group was mainly localized in the esophageal epithelium,mucosa and submucosa,while 8-OHdG expression in AF group almost covered the whole mucosa,indicating severe tissue oxidative damage in AF patients.RT-PCR and ELISA showed that the relative mRNA expression levels of 8-OHdG,MCP-1,IL-8 and TNF-α and their concentrations in serum increased significantly in non-AF group and AF group(peak in AF group)compared with the control group(all P<0.01).Pearson correlation analysis showed that the serum concentration of 8-OHdG was positively correlated with Demeester score and serum MCP-1,IL-8,TNF-α levels in AF group (P<0.01). Conclusion The expression of 8-OHdG and inflammatory factors (MCP-1,IL-8,TNF-α) and the concentration of blood in the esophageal mucosa of GERD complicated with AF patients were significantly increased,which may be closely related to the occurrence of AF induced by acid reflux.
文章编号:     中图分类号:    文献标志码:A
基金项目:新疆自然科学基金(2018D01C134)
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引用文本:
买买提艾力·艾则孜,买买提·依斯热依力,张为民,等.8-羟基脱氧鸟苷在胃食管反流病合并房颤患者食管组织中的表达及作用[J].中国临床研究,2019,32(9):1175-1180.

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