幽门螺杆菌菌株类型与儿童上消化道疾病的关系

目的：幽门螺杆菌（Helicobacter pylori,Hp）感染已被确立为是引起慢性浅表性胃炎和消化性溃疡的重要病因，是胃癌和胃黏膜相关性淋巴样组织（MALT）淋巴瘤的重要危险因素。Hp的致病性与毒力有关，而细胞毒素相关蛋白（CagA）和空泡毒素（VcaA）是Hp的主要毒力因子之一。该研究通过了解Hp菌株类型与儿童胃十二指肠疾病类型及胃窦黏膜病理组织学变化的关系，探讨Hp感染的分型诊断是否有助于判断儿童胃十二指肠疾病的严重程度。方法：采用免疫印迹法对115例有上消化道症状的患儿进行Hp的血清学分型，并行胃镜检查，观察胃十二指肠疾病类型。取胃窦黏膜经Harris配方苏木精染色观察胃窦黏膜病理组织学变化、亚甲基蓝染色观察Hp感染情况。结果：115例患儿中检出Hp Ⅰ型菌株84例（73.0%），中间型菌株21例（18.3%），Ⅱ型菌株10例（8.7%）；Ⅰ型菌株引起胃窦黏膜中、重度炎症分别为83例、1例；中间型菌株引起胃窦黏膜中度炎症21例；Ⅱ型菌株引起胃窦黏膜轻度炎症2例，中度炎症8例，经统计学处理，各型菌株在引起胃窦黏膜炎症程度上差异有显著性（χ2=15.444，P<0.01），Ⅰ型菌株感染引起胃窦黏膜炎症程度最重，Ⅱ型菌株感染引起胃窦黏膜炎症程度最轻；而在活动性、萎缩的发生率上，各型差异无显著性（P＞0.05）；在淋巴滤泡形成的发生率上，各型差异有显著性（χ2=10.171，P<0.01）。各型菌株引起胃镜下胃、十二指肠疾病类型的构成比无明显差异（P＞0.05）。结论：该地区儿童Hp感染以Ⅰ型菌株最为多见。各型菌株100%存在胃窦黏膜组织学改变。Ⅰ型菌株感染所致胃窦黏膜炎症程度最重，且引起淋巴滤泡形成的发生率最高。Hp感染的分型诊断无助于对儿童胃、十二指肠疾病类型的判断，但有助于对儿童胃、十二指肠疾病病情的判断，Ⅰ型菌株感染者需要更为积极的治疗，对于Hp感染的儿童无论其血清分型如何，均应引起重视，并长期随访。［中国当代儿科杂志，2007，9（3）：201-204］     

幽门螺杆菌细胞毒素相关蛋白、空泡毒素基因与儿童胃十二指肠疾病的关系

目的　探讨幽门螺杆菌 (Hp)细胞毒素相关蛋白 (cagA)、空泡毒素 (vacA)与儿童胃十二指肠疾病类型及胃黏膜炎症程度的关系。方法　采用免疫印迹法测定 88例Hp相关性慢性胃炎 (CG)、4 6例Hp相关性消化性溃疡 (PU)患儿血清cagA、vacA抗体 ,并观察胃黏膜病理变化。 结果　 1.CagA、vacA抗体总检出率分别为 85 .0 7%、91.0 4 % ,cagA抗体在CG与PU中检出率分别为 84 .0 9%与 86 .96 % ,两组相比无显著性差异 (P>0 .0 5 ) ;vacA抗体在CG与PU中检出率分别为 89.77%与 93.4 8% ,两组相比无显著性差异 (P >0 .0 5 )。 2 .134例Hp感染患儿cagA、vacA抗体均阳性 (Ⅰ型菌 ) 113例 ,cagA、vacA抗体均阴性 (Ⅱ型菌 ) 11例 ,cagA、vacA抗体仅一项阳性 (中间型 ) 10例 ,各型菌株在CG、PU中的检出率无明显差异 (P均 >0 .0 5 )。 3.113例Hp Ⅰ型菌株感染引起胃黏膜中重度炎症占 88.5 0 % ,而Ⅱ型菌株、中间型菌株感染引起胃黏膜中重度炎症分别为 4 5 .4 5 %及 5 0 .0 0 % ,两组有显著性差异 (P <0 .0 1)。结论　CagA、vacA与CG、PU发病均有关 ,不能作为区分Hp感染致不同胃十二指肠疾病的特异性指标。本地区儿童感染的Hp主要为cagA和vacA阳性的Ⅰ型菌株 ,能引起胃黏膜较重的炎症     

幽门螺杆菌与儿童慢性胃炎的关系

目的探讨幽门螺杆菌(Hp)感染与小儿慢性胃炎之间的关系。方法对具有上消化道症状、并经胃镜检查确诊为慢性胃炎112例患儿进行胃黏膜活检,病理组织学检查及快速尿素酶试验、改良Giemsa染色查找Hp。结果112例慢性胃炎患儿中,Hp阳性51例,Hp感染率为45.53%。胃黏膜组织炎症越重,Hp感染阳性率越高。Hp阳性组胃黏膜炎症较重。结论儿童时期Hp感染率较高,且随年龄增长而增高。Hp感染可加重胃黏膜组织炎症。     

幽门螺杆菌相关性胃肠粘膜病患儿血清CagA抗体、VacA抗体检测及其临床意义

为了解幽门螺杆菌（elicobacter pylori,H.pylori)相关性胃肠粘膜病患儿血清中细胞毒素相关基因抗原（CagA)、空泡毒素抗原（VasA)的有无及其临床意义，应用免疫印迹法对46例慢性胃炎和25例消化性溃疡患儿血清CagA抗体、VacA抗体进行了检测。结果：（1）慢性胃炎小儿血清H.Pylori CagA抗体（＋）、VacA抗体（＋）检出率为28．3％，消化性溃疡患儿为64．0％，两组比较差异有显著性（P＜0．05）；（2）对慢性胃炎炎症活动程度进行分组检测，中、重度急性活动性胃炎患儿中H.Pylori CagA抗体（＋）、VacA抗体（＋）检出率为50．0％，与轻症者比较差异有显著性（P＜0．05）。提示H.pylori菌株存在不同致病能力，CagA、VasA是致小儿H.Pylori相关性胃肠粘膜病重要的毒力因素；通过检测CagA、VacA抗体，可及时指导临床治疗。     

儿童再发性腹痛与幽门螺杆菌感染关系探讨

对１２３例非精神心里因素所致的再发性腹痛（ＲＡＰ）患儿进行胃镜检查及幽门螺杆菌（ＨＰ）检测。胃镜所见：正常１７例（１３８％），慢性胃炎（ＣＧ）６６例（５３７％），ＣＧ合并十二指肠球炎１３例（１０６％）、合并食管炎４例（３２％），消化性溃疡（ＰＵ）２２例（１７９％），幽门管狭窄１例（０８％）。采用三种方法检测ＨＰ：ＥＬＩＳＡ方法、ＰＣＲ技术及组织学染色找菌，ＨＰ阳性率５７７％。１２３例中６６例进行了病理学检查，观察到胃炎炎症程度与ＨＰ感染相关，６６例中胃窦粘膜活检正常６例，Ｇｉｅｍｓａ染色找菌ＨＰ全部阴性，轻度ＣＧ３７例Ｇｉｅｍｓａ染色ＨＰ阳性１１例（１１／３７），中重度２２例ＨＰ均为阳性。本组资料显示儿童ＲＡＰ多数存在器质性病变，并与ＨＰ感染有关。对非精神性ＲＡＰ、尤其血清ＨＰＩｇＧ抗体及胃液ＨＰＰＣＲ检测阳性者应进一步做胃镜检查以明确诊断。     

幽门螺杆菌细胞毒素相关蛋白与胃窦黏膜炎症程度、细菌定植密度的关系

目的探讨幽门螺杆菌(Hp)细胞毒素相关蛋白(CagA)与慢性胃炎患儿胃窦黏膜炎症程度、Hp定植密度的关系。方法对79例Hp相关性慢性胃炎患儿采用免疫印迹法检测血清CagA抗体,并行胃镜检查,取胃窦黏膜经HE及改良Giemsa 染色后观察胃窦黏膜炎症程度及Hp定植密度。结果79例Hp相关性慢性胃炎患儿血清CagA抗体阳性67例(84.81%),其中胃窦黏膜轻度炎症9例(13.43%),中重度炎症58例(86.57%),而12例血清CagA抗体阴性患儿胃窦黏膜轻度炎症7例(58 33%),中重度炎症5例(41 67%),两者差异有显著性(x2=10.076 P=0.002),而两组胃窦黏膜Hp定植密度无明显差异(H=0.246 P-0 884)。结论CagA与慢性胃炎患儿胃窦黏膜炎症程度有关.而与Hp在胃窦部的定植密度无关,CagA 阳性Hp菌株能引起胃窦黏膜较重炎症。     

幽门螺杆菌毒素与儿童胃十二指肠疾病关系的研究

目的 探讨幽门螺杆菌（Hp）毒素与儿童胃十二指肠疾病的关系及Hp毒素参与胃十二指肠粘膜病变的机制,并评价Hp毒素抗体检测的临床意义。方法 采用免疫印迹法测定39例Hp阳性和32例Hp阴性患儿血清多种Hp毒素抗体。观察胃十二指肠粘膜病理变化。结果 Hp阳性患儿,Hp毒素抗体相对分子质量为116000、30000、26500、19500和现症感染标志（CIM）的阳性率均为100％。相对分子质量为89000、61000、58000、37000和35000的阳性率分别为94．9％、87．2％、53．9％、87．2％和46．2％。HpI型菌株占94．9％,未检出Ⅱ型菌株。Hp阴性患儿各抗体的检出率为0％－28．1％。各种抗体在不同疾病之间的检出率无显著差异。细胞毒素相关蛋白（CagA）、空泡细胞毒素（VacA)和尿素酶A、D、E抗体阳性者胃十二指肠膜无一例正常,中重度炎症发生率为94．9％－97．3％。尿素酶B抗体阳性者胃粘膜中性粒细胞浸润比阴性者多见,差异有显著性。结论 本地区儿童主要感染HpI型毒力菌株,引起的胃十二指肠粘膜炎症较严重。尿素酶B抗体阳性提示胃粘膜有活动性炎症。CagA、VacA等Hp毒素抗体可能不是儿童十二指肠溃疡的特异标志物。     

幽门螺杆菌毒素因子与儿童胃十二指肠疾病的相关性研究

目的　研究贵阳地区儿童幽门螺杆菌感染的CagA蛋白及VacA蛋白的感染状况 ,以及不同Hp菌株类型与胃肠黏膜病理组织学改变的关系。方法　采用免疫印迹法 (WesternBlot)对 6 7例Hp阳性及 32例Hp阴性患儿血清进行Hp毒素因子的测定及血清学菌株分型 ,参照悉尼胃炎分类标准 ,对不同Hp菌株类型进行病理组织学对比研究。结果　本地区Ⅰ型高毒力Hp菌株检出率 6 8.6 % ,中间型Hp菌株为 2 6 8% ,Ⅱ型Hp低毒力菌株为 4 4 %。Ⅰ型Hp菌株 1 0 0 %存在胃肠黏膜组织学改变 ,胃窦黏膜以中度炎症为主 ,占 73 9% ,重度炎症占 1 1 % ,活动性占 73 9%。十二指肠球部黏膜以中 重度炎症为主 ,占77 3% ,活动性占 6 6 4 %。中间型Hp菌株 72 %存在黏膜组织学改变 ,胃窦黏膜以轻度炎症为主 ,占 5 5 6 % ,活动性占 5 5 % ,十二指肠球部黏膜以轻 中度炎症为主 ,占 5 5 1 % ,活动性占 1 1 1 %。Ⅰ型Hp菌株与中间型Hp菌株在致黏膜炎症改变程度及活动性方面有差异性 (P <0 0 5 )。在淋巴滤泡形成方面 ,Ⅰ型Hp菌株较中间型Hp菌株有显著性差异 (P <0 0 1 )。结论　本地区Hp感染菌株类型以Ⅰ型为主 ,占 6 8 6 % ,同时存在 2 6 8%的中间型菌株及 4 4 %的Ⅱ型菌株的感染。Ⅰ型Hp菌株及中间型菌株在黏膜炎症程度及活动性上有差异性     

儿童幽门螺杆菌细胞毒素相关基因A检测的意义

目的探讨儿童幽门螺杆菌(Hp)细胞毒素相关基因A(cagA)的流行情况,分析其与胃十二指肠疾病的关系。方法对80例患儿经胃黏膜快速尿素酶试验和Warthin-Starry银染色,聚合酶链式反应(PCR)法检测Hp尿素酶C基因及血清抗Hp-IgG确诊为Hp感染儿童采用PCR法检测胃黏膜cagA。结果80例患儿胃黏膜Hp菌株应用cagA的5对不同引物分别扩增ca-gA DNA 400、280、349、298 bp和191 bp 5个片段,cagA检出率分别为43.8%、20.0%、55.0%、32.5%和61.2%,它们之间有显著性差异。cagA总检出率为83.7%。轻度与中重度炎症cagA检出率无显著性差异。慢性浅表性胃炎及消化性溃疡两组cagA检出率无显著性差异。结论南宁地区儿童Hp以cagA阳性为主。cagA基因与胃黏膜炎症程度无关,且cagA基因不能作为南宁地区Hp菌株毒力强弱的指标。     

幽门螺杆菌感染与儿童胃炎关系探讨

为进一步研究幽门螺杆菌（Helicobacter pylori,H.pylori)感染与儿童胃炎的关系，对我科1998年至2000年间500例3岁－15岁儿童胃镜活检组织进行组织学和H.pylori观察，按Sydney胃炎标准对病变分级，分析和探讨H.pylori感染与儿童胃炎发展变化的关系。结果表明：40.4%的儿童胃炎与H.pylori感染有关；而且炎症的程度、淋巴滤泡的形成、嗜酸细胞增多及幽门腺萎缩明显高于无H.pylori感染的儿童胃炎。提示上海地区儿童胃炎有很高的H.pylori感染率，H.pylori感染与儿童胃炎关系密切，儿童H.pylori胃炎的胃粘膜病理变化比非H.pylori感染者严重。     

Gastric inflammation is enhanced in children with CagA-positive Helicobacter pylori infection

BACKGROUND: Helicobacter pylori infection is likely to be acquired at an early age. The factors leading to active inflammation in childhood, however, are largely unknown. SUBJECTS AND METHODS: We determined the CagA status, the best characterized virulence factor of H. pylori, and serum antibodies of IgG and IgA classes to H. pylori in 39 infected children. RESULTS: Mononuclear cell infiltration in the antrum but not in the gastric body was more intense in CagA-positive children than in CagA-negative children. The degree of polymorphonuclear cell infiltration on the other hand was independent of the CagA status. The antibody titers of IgG and IgA classes to H. pylori were higher in CagA-positive than in CagA-negative infections (P<0.001 and P<0.01, respectively). IgG antibody titers to H. pylori correlated directly with the density of mononuclear and polymorphonuclear cell infiltration in the gastric antrum but not in the gastric body. CONCLUSION: H. pylori-infected children with CagA antibodies seem to have a more severe inflammation in the gastric antrum than CagA-negative children as shown by an increase in the density of antral mononuclear cells. A finding of higher serum antibody titers to H. pylori in CagA-positive children may be related to this enhancement of inflammation.     

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.     

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.     

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.     

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］     

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.