摘要
目的探讨幽门螺杆菌(Hp)毒力因子基因型与儿童胃十二指肠疾病、胃黏膜病理学改变程度的关系。方法回顾性队列研究。研究时间为2020年5至10月,研究对象为2012年4月至2014年12月因消化道不适症状就诊于浙江大学医学院附属儿童医院,胃镜检查确诊为胃十二指肠疾病、胃黏膜Hp培养阳性的68例患儿的冻存菌株。复苏Hp菌株提取DNA后进行PCR扩增和琼脂糖凝胶电泳,确定细胞毒素相关蛋白A(cagA)、空泡细胞毒素A(vacA)(s1a、s1b/s2,m1/m2)、外膜炎性蛋白A(oipA)、血型抗原结合黏附素(babA2)、十二指肠溃疡促进因子A(dupA)基因的检出率,对oipA基因进行测序,判定基因状态。根据胃镜诊断结果、胃黏膜病理结果进行分组,分析各毒力因子基因型的检出率在不同组患儿之间的差异,组间比较采用χ^(2)检验或Fisher确切概率法。结果完成基因测定的68株Hp菌株来自68例Hp感染的胃十二指肠疾病患儿,根据胃镜诊断结果分为浅表性胃炎47例和消化性溃疡21例。根据胃黏膜病理炎症程度分为轻度8例和中重度60例;按胃黏膜病理炎症活动性分为活动性组61例和无活动性组7例。cagA、vacA、vacA s1/m2、功能性oipA、babA2和dupA 6种毒力因子基因的检出率分别为100%(68/68)、100%(68/68)、94%(64/68)、99%(67/68)、82%(56/68)、71%(48/68);6种毒力因子基因在浅表性胃炎组检出率分别为100%(47/47)、100%(47/47)、96%(45/47)、98%(46/47)、81%(38/47)、70%(33/47),在消化性溃疡组分别为100%(21/21)、100%(21/21)、90%(19/21)、100%(21/21)、86%(18/21)、71%(15/21),各基因型检出率在两组患儿间差异均无统计学意义(均P>0.05);6种毒力因子基因在胃黏膜炎症程度轻度组分别为8/8、8/8、8/8、7/8、7/8、5/8,在胃黏膜炎症程度中重度组分别为100%(60/60)、100%(60/60)、93%(56/60)、100%(60/60)、82%(49/60)、72%(43/60),各基因型检出率在两组患儿间差异均无统计学意义(均P>0.05);6种毒力因子基因在胃黏膜炎症活动性组分别为100%(61/61)、100%(61/61)、93%(57/61)、98%(60/61)、82%(50/61)、72%(44/61),在无活动性组分别为7/7、7/7、7/7、7/7、6/7、4/7,各基因型检出率在两组患儿间差异均无统计学意义(均P>0.05)。4种或5种毒力因子基因阳性组合检出率在不同组患儿之间的差异均无统计学意义(均P>0.05)。结论cagA、vacA、vacA s1/m2、功能性oipA、babA2、dupA基因与儿童浅表性胃炎和消化性溃疡及胃黏膜病理炎症程度和活动性的关系均不明显;cagA、vacA、oipA、babA2、dupA的不同基因组合对于预测儿童Hp感染的临床结局没有显著作用。
Objective To investigate the association between Helicobacter pylori(Hp)virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases.Methods This retrospective cohort study was conducted from May 2020 to October 2020.The frozen strains of Hp,which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children′s hospital of Zhejiang University School of Medicine from April 2012 to December 2014,were resuscitated.After extracting DNA from these Hp strains,PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A(cagA),vacuolating cytotoxin A(vacA)(s1a、s1b/s2,m1/m2),outer inflammatory protein A(oipA),blood group antigen binding adhesin(babA),duodenal ulcer promoting protein A(dupA)genes;oipA genes were sequenced to determine the gene status.The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology.The detection rates of various virulence factor genotypes among different groups were compared usingχ^(2) tests or Fisher′s exact tests.Results The 68 Hp strains all completed genetic testing.According to the diagnostic findings of gastroscopy,the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer.Regarding the pathological changes of gastric mucosa,8 cases were mild,and 60 cases were moderate and severe according to the degree of inflammation;61 cases were active and 7 cases inactive according to the activity of inflammation.The overall detection rates of cagA,vacA,vacA s1/m2,functional oipA,babA2,and dupA virulence factor genes were 100%(68/68),100%(68/68),94%(64/68),99%(67/68),82%(56/68),and 71%(48/68),respectively.In the superficial gastritis group,their detection rates were 100%(47/47),100%(47/47),96%(45/47),98%(46/47),81%(38/47),and 70%(33/47),respectively;in the peptic ulcer group,their detection rates were 100%(21/21),100%(21/21),90%(19/21),100%(21/21),86%(18/21),and 71%(15/21),respectively.There was no statistically significant difference between the two groups(all P>0.05).In the mild gastric mucosa inflammation group,the detection rates of the above six genotypes were 8/8,8/8,8/8,7/8,7/8,and 5/8,respectively;and in the moderate to severe inflammation groups,the detection rates were 100%(60/60),100%(60/60),93%(56/60),100%(60/60),82%(49/60),and 72%(43/60),respectively,with no statistically significant difference between the two groups(all P>0.05).In the active inflammation group,the detection rate of six genotypes were 100%(61/61),100%(61/61),93%(57/61),98%(60/61),82%(50/61),and 72%(44/61),respectively;and in the inactive inflammation group,they were 7/7,7/7,7/7,7/7,6/7,and 4/7,respectively.Again,there was no statistically significant difference between the two groups(all P>0.05).There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups(all P>0.05).Conclusions CagA,vacA,vacA s1/m2,functional oipA,babA2,and dupA genes are not associated with superficial gastritis and peptic ulcer in children,or with the degree and activity of gastric mucosa pathological inflammation.Different gene combinations of cagA,vacA,oipA,babA2,and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.
作者
应晶晶
舒小莉
龙高
江米足
Ying Jingjing;Shu Xiaoli;Long Gao;Jiang Mizu(Gastrointestinal Laboratory,Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,National Children′s Regional Medical Center,Hangzhou 310052,China;Department of Gastroenterology and Pediatric Endoscopy Center,Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,National Children′s Regional Medical Center,Hangzhou 310052,China)
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2023年第9期827-832,共6页
Chinese Journal of Pediatrics
基金
浙江省重点研发计划(2021C03064)。
关键词
螺杆菌
幽门
毒力因子类
胃炎
消化性溃疡
儿童
Helicobacter pulori
Virulence factors
Gastritis
Peptic ulcer
Child
