幽门螺杆菌感染儿童胃黏膜细胞凋亡相关蛋白的研究

目的：旨在研究儿童胃黏膜细胞凋亡相关蛋白p53和Bax的表达水平与幽门螺杆菌（Hp）感染的关系。方法：采用免疫组化法检测了33例胃黏膜病变儿童胃黏膜上皮细胞中p53和Bax表达水平,并采用快速尿素酶试验和组织病理学检测两种方法检查这些病例的Hp感染情况。结果：在17例Hp阳性组织标本中,15例（88%）p53表达阳性,而在16例Hp阴性组织标本中,9例（56%）呈阳性。分析Bax的表达水平发现,在17例Hp阳性组织标本中,13例（76%）标本Bax表达呈阳性,而在16例Hp阴性组织标本中,6例 （38%）呈阳性。统计学分析显示,Hp阳性标本的p53和Bax表达水平要明显高于Hp阴性标本（P<0.05）。结论：儿童期Hp感染与胃黏膜上皮细胞p53蛋白和Bax蛋白过度表达密切相关。［中国当代儿科杂志,2010,12（2）：110-112］     

Cytokines in the gastric mucosa of children with Helicobacter pylori infection

AIM: Few studies have looked at the cytokine profile in gastric mucosa in children with Helicobacter pylori infection. This study investigated cytokines and their effects on histological abnormalities in the gastric mucosa of children with H. pylori infection. METHODS: The levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-8 proteins were measured in biopsy specimens from the gastric antrum and corpus of children with H. pylori infection, and related to inflammatory cell infiltrations. RESULTS: The antral and corporal mucosal levels of IFN-gamma and IL-8 proteins were significantly higher in children with H. pylori infection than in uninfected children, but there was no such difference in the levels of IL-4 protein. The antral mucosal level of IL-8 protein was significantly higher than the corporal mucosal level of IL-8 protein in the infected children. Inflammatory cell infiltration was significantly higher in the infected children than in the uninfected children, but there were no significant correlations between mucosal cytokine levels and inflammatory cell infiltrations. CONCLUSION: The results suggest that the predominant Th1 cytokine response and enhanced IL-8 production in the mucosa may be involved in the gastric inflammation seen in children infected with H. pylori, as well as in adult patients.     

Microarray analysis of gastric mucosa among children with Helicobacter pylori infection

Background: Although initial infection with Helicobacter pylori may occur before 5 years of age, the pediatric mucosal immune response against H. pylori is not clear. The aim of the present study was to evaluate immune responses in the H. pylori‐infected gastric mucosa of children using microarray and real‐time polymerase chain reaction (PCR) analysis of pediatric gastric samples. Methods: Gastric samples were obtained from 12 patients undergoing routine endoscopy of chronic abdominal complaints. Six patients (three boys, three girls) aged 10.1–14.6 years had evidence of H. pylori infection, and the remaining six (three boys, three girls) aged 10.3–15.5 years had no evidence of infection and presented no histological changes associated with gastritis. Microarray and real‐time PCR analyses were performed, and the changes in gene expression‐related immune response were also analyzed. Results: Using microarray analysis, the total number of significantly upregulated and downregulated genes (fold change >5, P < 0.01) was 21 in the antrum and 16 in the corpus when comparing patients with or without infection. Using real‐time PCR, the expression of lipocalin‐2 (Lcn2), C‐C motif chemokine ligand (CCL) 18, C‐X‐C motif chemokine ligand (CXCL) 9 and CXCL11 was upregulated, while the expression of pepsinogen (PG) I and PGII was downregulated when comparing patients with or without infection. Conclusions: Lcn2, CCL18, CXCL9, CXCL11, PGI and PGII play important roles in childhood H. pylori infection.     

Lewis antigen expression in gastric mucosa of children: relationship with Helicobacter pylori infection

OBJECTIVE: Lewis epithelial antigen expression has a role in Helicobacter pylori adherence, presumably mainly in cagA-positive strains. The authors investigated whether Lewis antigen expression in children's gastric mucosa was associated with H. pylori infection, cagA status, patient age, or presence of duodenal ulcer (DU). METHODS: The expression of Lewis A (Le(a)), B (Le(b)), X (Le(x)), and Y (Le(y)) was detected by immunohistochemistry in the antral and oxyntic mucosae of 70 children. Children were divided in four age groups (<4 years; 4-8 years; 9-12 years; and 13-18 years). RESULTS: Forty-seven of the 70 children had H. pylori and 17 had DU. The cagA status was determined by polymerase chain reaction in 34 patients. Le(a) and Le(b) were expressed in 64% and 44% of the patients, respectively; Le(x) and Le(y) were expressed in the glands in all of the patients and in the superficial epithelium. Le(b) expression was more common among patients without H. pylori (15/23, 65%) than in those with H. pylori (16/47, 34%) (P = 0.03). In noninfected patients, Le(b) and superficial Le(y) expression were associated with increased age. Le(b) expression was more common in patients with chronic gastritis than in those with DU. Le(x) superficial expression was significantly associated with DU in patients with H. pylori. CONCLUSION: In children, the expression of Le(b) and Le(y) in the superficial gastric epithelium depends on age. Other receptors, such as Le(x), may have a role in H. pylori colonization, especially in patients with DU. Studies assessing the expression of Lewis antigens in children may contribute to an understanding of the mechanisms of acquisition of H. pylori infection.     

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目的探讨幽门螺杆菌(HP)感染对不同年龄组儿童慢性胃炎胃黏膜病理变化的影响。方法 2007年1月至2010年12月,对上海交通大学医学院附属瑞金医院1634例反复上消化道症状儿童行电子胃镜检查,取胃窦部黏膜组织检测HP,按1996年悉尼标准进行病理评分,分析HP感染与炎症严重程度及活动性的关系。并根据年龄分为4组:<4岁组69例,4～<7岁组313例,7～<11岁组706例,11～18岁组546例,比较各组HP感染率、活动性病变发生率以及淋巴滤泡检出率的差异。结果 1634例患儿中HP阳性524例(32.1%),阳性率随年龄增长而升高。HP阳性患儿活动性炎症、中重度炎症、中性粒细胞浸润、淋巴细胞重度浸润和淋巴滤泡的检出率均高于阴性者(P<0.01)。胃黏膜病理示慢性浅表性胃炎(CSG)中、重度炎症及慢性萎缩性胃炎(CAG)中度炎症的发生率,HP阳性患儿均高于阴性者(P<0.01)。除婴幼儿组外,各年龄组HP感染患儿的活动性病变发生率和淋巴滤泡检出率均显著高于HP阴性者(P<0.05)。结论儿童HP感染率随年龄增长而升高。HP感染与胃黏膜炎症严重程度、活动性炎症发生率以及滤泡样改变均密切相关,与慢性胃炎不同病理类型的严重程度也密切相关。     

幽门螺杆菌感染儿童胃十二指肠粘膜IL-8含量的研究

检测幽门螺杆菌 (H.pylori)感染儿童的胃、十二指肠粘膜中IL_8含量的变化 ,以探讨其在H.pylori相关性胃十二指肠疾病中的机理。在胃镜下取胃窦及十二指肠球部粘膜活检标本 ,用ELISA法测定粘膜中IL_8的含量。结果 :H.pylori阳性者胃粘膜IL_8为 (24.66～177.77)pg/mg,H.pylori阴性者为(2.94～12.98)pg/mg,两者相比t=12.34,P<0.01 ;H.pylori阳性者十二指肠粘膜IL_8为(12.98～177.77)pg/mg,H.pylori阴性者为(2.04～10.43)pg/mg,两者相比t=7.18,P<0.01。活动性胃炎胃粘膜IL_8为(12.98～177.77)pg/mg,非活动性胃炎为(2.04～10.43)pg/mg,两者相比t=10.66,P<0.01;活动性胃炎十二指肠粘膜IL_8为(5.28～47.76)pg/mg ,非活动性胃炎为(3.19～8.14)pg/mg ,两者相比t=6.52,P<0.01。说明H.pylori阳性和活动性胃炎胃粘膜及十二指肠粘膜IL_8含量均较高。提示H.pylori感染时 ,IL_8在胃十二指肠粘膜局部大量中性粒细胞浸润中可能有重要作用。     

幽门螺杆菌菌株类型与儿童胃粘膜炎症程度的关系探讨

目的探讨幽门螺杆菌菌株类型与儿童胃粘膜炎症程度之间的关系。方法采用免疫印迹法测定134例幽门螺杆菌感染患儿血清细胞毒素相关蛋白(CagA)、空泡毒素(VacA)抗体,对幽门螺杆菌进行分型,并观察胃粘膜病理变化。结果CagA、VacA抗体总检出率分别为85.07%(114/134例)、91.04%(122/134例),检出幽门螺杆菌I型菌株113例,Ⅱ型菌株11例,中间型菌株10例,各型菌株感染引起胃粘膜中重度炎症分别为100例(88.50%)、5例(45.45%)、5例(50.00%),I型菌株与II型菌株、中间型菌株比较,差异有显著性(Hc=20.05,P<0.01)。结论幽门螺杆菌菌株类型与儿童胃粘膜炎症程度有关,I型菌株能引起较重的胃粘膜炎症。     

The effect of non-steroidal anti-inflammatory drugs and Helicobacter pylori infection on the gastric mucosa in children with upper gastrointestinal bleeding

Objective  

To study the effect of non-steroidal anti-inflammatory drugs (NSAID) and of Helicobacter pylori infection on the gastric mucosa in children with upper GI bleeding (UGIB).     

Helicobacter pylori infection, histopathological gastritis and gastric epithelial cell apoptosis in children

AIM: Features of gastritis and gastric epithelial cell apoptosis in children infected with Helicobacter pylori genotypes are seldom studied. Therefore, we investigated the relationship between vacA genotypes and the severity of gastritis, and gastric epithelial cell apoptosis in H. pylori-infected children. METHODS: Antral biopsies from 52 children infected with H. pylorivacA genotypes (s1a/m1 = 17, s1a/m2 = 21 and s2/m2 = 14) were analysed for severity of gastritis on histopathology. Fifteen biopsies infected with different vacA genotypes were studied for gastric epithelial cell apoptosis by terminal uridine deoxynucleotidyl nick-end labelling. RESULTS: Children infected with the s1a/m1 and s1a/m2 vacA genotypes had higher severity of chronic inflammation than the s2/m2 genotype (s1a/m1 vs s2/m2, p=0.05; s1a/m2 vs s2/m2, p=0.01). The vacA s1a allele was more independently associated with severe chronic inflammation than the s2 allele (p=0.02). Children infected with the s1a/m1 and s1a/m2 strains had higher gastric epithelial cell apoptosis than the s2/m2 strain (s1a/m1 or s1a/m2 vs s2/m2, p<0.0001). CONCLUSION: The s1a/m1 and s1a/m2 H. pylorivacA genotypes have significantly higher association with severe chronic gastritis and gastric epithelial cell apoptosis than the s2/m2 genotype in children. The role of H. pylorivacA genotypes and their allelic subtypes in relation to pathogenicity and disease potential in children needs further studies.     

Growth in children with Helicobacter pylori infection and dyspepsia.

AIMS: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. METHODS: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. RESULTS: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. CONCLUSION: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection.     

Helicobacter pylori infection in children

A number of scientific breakthroughs since H pylori first became recognized as a human pathogen have increased our understanding of the pathogenesis of gastroduodenal disease. In particular, advances in molecular bacteriology and the complete sequencing of the H pylori genome in 1999, and soon thereafter the human genome, provide tools allowing better delineation of the pathogenesis of disease. These molecular tools for both bacteria and host should now be applied to multicenter pediatric studies that evaluate disease outcome. More recent developments indicate that a better understanding of the microbial-host interaction is critical to furthering knowledge with respect to H pylori-induced diseases. Studies are needed to evaluate either DNA-based or more traditional protein-based vaccines, to evaluate more specific antimicrobials that confer minimal resistance, and to evaluate probiotics for the management of H pylori infection. Multicenter multinational studies of H pylori infection in the pediatric population, which include specific, randomized controlled eradication trials, are essential to extend current knowledge and develop better predictors of disease outcome.     

Helicobacter pylori infection in children

Helicobacter pylori colonizes the human stomach, especially during childhood. However, a variety of H. pylori strains exists, with major differences in virulence characteristics which probably account for different clinical symptoms, and the majority of infected subjects remains asymptomatic. Helicobacter pylori infection is correlated with socioeconomic conditions and hygienic circumstances, resulting in an extremely high prevalence in children in developing countries. Commercial screening tests are not capable of separating the more virulent strains (type I with vacuolating toxin VacA and CagA protein) from the less virulent strains (type II, VacA and CagA negative). Type I strains, but not type II, are associated with an increased risk for duodenal ulcer and gastric cancer. Therefore, future screening tests and vaccinations should focus on the type I strains.     

儿童幽门螺杆菌感染与HLA-DQB1等位基因遗传多态性研究

目的　研究HLA -DQB1基因位点上是否存在幽门螺杆菌(H .pylori)感染及其相关胃炎的易感基因或抵抗基因,从免疫遗传角度探讨H .pylori感染后临床结局多样性的可能发生机制。方法　对1 999年9月至2 0 0 0年7月上海第二医科大学附属瑞金医院收治的1 3 3例慢性胃炎及80名健康儿童(对照组) ,进行H .pylori检测,应用PCR SSO杂交方法确定其HLA -DQB1等位基因型别。结果　80名对照组儿童中H .pylori阳性3 3名,H .pylori阴性47名;1 3 3例慢性胃炎患儿中,H .pylori阳性85例,H .pylori阴性48例。DQB1 0 3 0 3 2等位基因频率在血清学H .pylori阳性者中低于血清学H .pylori阴性的健康儿童( 1 0 . 61 %vs 2 5. 53 % ,P <0 . 0 5)。DQB1 0 60 2等位基因频率在H .pylori阳性胃炎患儿低于H .pylori阴性胃炎患儿( 4 . 71 %vs 1 2 . 50 % ,P <0 . 0 5)。结论　DQB1 0 3 0 3 2对H .pylori感染可能具有抵抗保护作用,DQB1 0 60 2缺乏可能是H .pylori相关性胃炎发生的宿主遗传因素。