反流对食管黏膜细胞凋亡相关基因表达的影响  

Experimental study on the effects of gastroesophageal reflux on the expressions of apoptosis-related gene in esophageal mucosal cells

作　　者：张萌[1] 黄刚[1] 周志刚[1] 杨金良[1] ZHANG Meng;HUANG Gang;ZHOU Zhigang(The Third Hospital of Hebe Medical University,Hebei,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第三医院胸外科

出　　处：《河北医药》2019年第17期2580-2584,共5页Hebei Medical Journal

摘　　要：目的观察胃及十二指肠液反流对食管上皮细胞凋亡相关基因表达的影响及与黏膜损伤的关系,探讨反流物致食管黏膜损伤的分子机制。方法选用健康雄性SD大鼠,分为单纯胃食管反流(G组)、十二指肠混合食管反流(DG组)及假手术对照组(C组)。光镜下观察3组大鼠术后不同时期食管黏膜上皮的病理变化,免疫组化法检测食管上皮肿瘤坏死因子-α(TNF-α)、Caspease-3、Survivin等基因的表达。结果光镜下,随造模时间延长,G组和DG组大鼠食管黏膜病变逐渐加重,DG组病变较同期G组明显加重,术后24周开始出现非典型增生。免疫组织化学法检测显示,G组、DG组与同期C组相比,食管黏膜上皮细胞TNF-α、Caspease-3表达明显上调(P<0.05),且DG组在28周和32周时TNF-α、Caspease-3表达较同期G组均明显增强(P<0.05)。C组食管黏膜上皮未见Survivin表达,G组在28、32周及DG组的各时间点Survivin均有明显的阳性表达(P<0.05)。结论胃酸反流、十二指肠液反流等刺激引起的食管黏膜损伤,其作用机制是一系列凋亡相关基因蛋白表达异常诱发食管黏膜上皮细胞的凋亡所致。Objective To investigate the effects of gastroesophageal reflux on the expressions of apoptosis-related gene in esophageal mucosal cells,and to explore possible molecular mechanism.Methods Two hundred healthy male SD(Sprague-Dawley)rats were randomly divided into 3 groups:simple gastroesophageal reflux group(group G,n=80),mixed gastric and duodenal reflux group(group DG,n=80)and sham-operation group(group C,40 rats).The pathological changes of esophageal mucous membrane were examined by light microscopy.The expression levels of TNF-α,Caspase-3 and Survivin were detected by immunohistochemical staining.Results By light microscopy,the pathological changes of esophageal mucosal of rats in group G and group DG were gradually aggratated with the time prolongation after modeling.And atypical hyperplasia could be observed at 24h after operation.The immunohistochemistry results showed that as compared with those in group C,the expression levels of TNF-αand Caspase-3 were significantly up-regulated in group G and group DG(P<0.05).Moreover the expression levels of TNF-αand Caspase-3 in group DG at 28w and 32w after operation were significantly higher than those in group G(P<0.05).In addition Survivin expression was not found in group C,however,which was observed in group G at 28w and 32w after operation and in group DG at all the time points(P<0.05).Conclusion It is indicated that various stimulus,including gastric acid reflux and duodenal liquid reflux,can resul in esophageal mucomembranous injury of rats,and its action mechanism may be related with the esophageal mucosal epithelial cells apoptosis induced by the expression abnormality of apoptosis-related gene proteins.

关 键 词：胃酸反流 十二指肠液反流 反流性食管炎 TNF-α Caspase-3 Survivin 

分 类 号：R571[医药卫生—消化系统]