摘要：目的对胃病高发区的西安地区城市及农村自然人群Hp及(CagA-Hp)感染状况进行血清流行病学调查，以期了解各年龄段Hp及CagA-Hp感染状况以及与胃癌等胃疾病的关系。方法对胃癌高发区的西安地区城市及农村自然人群2134人及525例胃病患者进行现况调查。并使用斑点金免疫渗滤法(DIGFA)对被调查者末梢血血清行抗Hp-尿素酶IgG(抗HpU-lgG)及抗Hp-CagA-IgG检测，检测结果进行统计学处理。感染率用百分数表示，做x2检验，P＜0．05为差异有显著意义。结果我们首次采用DIGFA方法对胃癌高发地区的西安地区自然人群包括婴幼儿在内的大样本人群及胃病患者进行抗Hp-CagA-lgG及抗HpU-lgG的血清流行病学调查，显示了西安地区0岁-60岁Hp感染与CagA-Hp感染年龄分布的全貌．其结果显示西安地区Hp感染的特点为：①可分为剧增期．缓增期．及平坦期．而且剧增期明显提前而且持续时间短(2岁～3岁年龄段)，缓增期不明显，5岁～6岁己接近平坦期(Hp感染率达50％左右)，②西安地区Hp的平均感染率为54．1％(31．1％～65．7％)，其中CagA+Hp感染率占23．2％(12．5％～29．3％)，城市及农村Hp与CagA+Hp感染率差异无显著意义(X2=0．01；2．85.P＞0．05)，③自然人群各年龄组中CagA+Hp感染率占Hp总感染率的比值相对固定，约为30％～50％④各种胃病患者CagA+Hp感染率明显升高，与自然人群者相比较，差异有非常显著意义(x”=27．96：139．98；183.40；155．49；133．29 p＜0.001)，⑤慢性萎缩性胃炎、十二指肠球部溃疡、胃溃疡、胃癌患者之间CagA+Hp感染率相比，差异无显著意义(P＞0.05)．结论西安地区(胃癌高发区)Hp感染率(约60％)较高，而且Hp感染高峰在较早年龄段(2岁～3岁年龄段)出现，各种胃病患者CagA+Hp感染率明显升高，提示：cagA+Hp期感染可能是西安地区胃癌等胃疾病发生的重要因素之一。Hp可能起着先导作用，CagA+Hp感染可能是作为损伤胃粘膜的启动因子参与了胃粘膜的早期损伤。

Seroepidemiological study of Hp and CagA+Hp infection

Li Zhang , Xiao Jun Yan,Ling Xia Zhang ,Feng Chan Han ,Ning Xia Zhang ,Yu Hou(Department of Gastroenterology,Xi'an Centre Hospital,Xi'an 710003,Shaanxi province,China)

Abstract：AIM to investigate-Hp and CagA+ Hp infecticn in persons with different age and the relationship between the infection and stomach diseases and stomach carcinoma by serum epidemic survey of the infection of Hp and CagA+ Hp in the city and country of Xi'an where the incidance of stomach carcinoma is very high.METHODS A natural population of 2134 and 525 patients with stomach diseases living in the city and country of Xi'an were surveyed. Dot immunogold filtration assay (DIGFA) was also used to detect anti-Hp-urease lgG (anti-Hp-U-lgG) and anti-Hp-CagA-lgG in the peripheral blood.The detection results were processed statistically. The x2-test of infection rate showed that P＜0.05.RESLTS The DIGFA method was first used to survey the anti-Hp-CagA-lgG and anti-Hp-U-lgG in large sample opulation (including infants) and the patients suffering stomach diseases in xi'an. The results manifested thewhole distribution of the infection of Hp and cagAt+Hp among the people ranging in age from 0-60 years, which showed the following features of the infection of Hp in Xi'an. ①The whole infection could he separated into three phases, "acutely-increasing-stage ","remission-stage" nd "smooth-stage". The acutely-increasing-phase was sharply set ahead and lasted shorter (among 2-3 years old people), the remission phase was not significant, and smooth stage was reached by 5-6 years of age with on infection rate of 50%. ② The average infection rate in Xi'an was 54.1% (31.1%-65.7%) among which the infection of cagA+ Hp accounted for 23.2% (12.5% -29.3%). The difference between the infection of Hp and CagA+ Hp in city and the infection in country was notsigeificant (x2=0.01, 2.85; P＞0.05).③ In the natural population, the ratio of the infection rate of CagA+Hp to the whole infection of Hp among different age groups was relatively constant, about 30%-50%. ④ The infectionrate of CagA+ Hp among all kinds of stomach diseasepatiants rose sigeificantly (x2= 27.96; 139,98; 183.40;155.49; 133.29. P＜0.001) as compared with the infection rate in natural population. ⑤ The difference of the infection rate among the patients suffering with chronic atrophic gastritis, duodenal ulcer, gastric ulcer andstomach carcinoma was not significant ( P ＞0.05). CONCLUSION The infection rate in Xi'an was rather high(about 60%) and the peak of the infection of Hp was reached in early years (2-3 years old) and the infection rate of CagA+ Hp was sharply increased in the patients with any stomach diseases, which implied that the enduring infection of CagA+ Hp was probablly an important factor for the stomach diseases such as stomach carcinoma in Xl'an. Hp could he an inducer and CagA+Hp infection involved in the early injury of stomach mucous membrane probably could do harm as a"promotion factor" to stomach mucous membrane.

Keywords：Helicobacter infections;cytotoxin associated protein; seroepidemiological study; stomach neoplasms; stomach diseases

0引言20世纪80年代以来，幽门螺杆菌(Hp)与胃癌的关系已受到广泛关注。世界卫生组织已将Hp列为Ⅰ类致癌物质[1]．已有的流行病学调查表明，Hp感染率随年龄增长而上升，发展中国家比发达国家高，并与社会经济状况，种族等因素有关[2]．近年来深入的研究发现，具有细胞毒素相关蛋白A(CagA)的Hp感染者发展成为萎缩性胃炎及胃癌的危险性是CagA阴性菌株感染者的两倍，CagA可能是胃癌发生的重要因素之一[3，4]．因此开展Hp感染的流行病学调查，特别是对CagA阳性菌株感染的流行病学调查研究，对胃癌的防治具有深远的意义，我们采用斑点金免疫渗滤法(DIGFA)，对胃癌高发区(西安地区)城市及农村自然人群Hp及cagA+亚型Hp感染状况进行血清流行病学调查，以了解各年龄段Hp感染及cagA+亚型Hp感染状况及其与胃癌等胃疾病的关系。1材料和方法1．1材料①自然人群我们采用分层整群随机抽样方法对西安地区(胃癌高发区)城市及农村自然人群进行普查。市区人群：按西安市人口构成比和市区街道分布，从接受检查的工厂、机关、学校和托儿所的人群中抽选1118例，其中男565例，女553例．市郊人群：从西安市附近郊县选3个乡，分层随机抽取1～2个行政村，整村普查．共1016例，其中男406例，女510例．②病例组：为西安市中心医院1998-03／1998-12经内镜及病理检查确诊的连续病例，共525例，其中慢性浅表性胃炎(CSG)122例，慢性萎缩性胃炎(CAG)118例，胃溃疡(GU)100例，十二指肠溃疡(DU)100例，胃癌(GCA)85例。1．2方法采用问卷调查方式，对性别、年龄、民族、职业、居住地、Hp及CagA-Hp感染等因素进行现况调查，问卷完后采集末梢血100μL，分离血清后于-20°C冷藏备用。1．2．1DIGFA实验方法在免疫渗滤板膜中央加洗 涤液一滴，待渗入；将待检血清5μL逐滴加于膜中央，待渗入后再加洗涤液3滴；将胶体金标记物15μL逐滴加入膜中央，待渗入后再加洗涤液3滴；结果判定：膜中央出现红色斑点为阳性，否则为阴性。1．2．2血清抗耶Hp-CagA-IgG采用第四军医大学全军基因诊断技术研究所与西安市中心医院消化科共同研制的斑点金免疫渗滤试验检测抗-HpCagAIgG试剂盒，重组抗原来源于幽门螺杆菌标准菌株ATCC53726．该试剂盒敏感性为94％，特异性为98％[5]．1．2．3血清抗Hp-尿素酶lgG采用福建三强生物化工有限公司生产的金标渗滤斑点法试剂盒检测抗HpU-IgG，其敏感性为95％，特异性为96％。统计学处理自然人群中Hp感染率及CagA-Hp感染率用百分数表示，并用西安市人口年龄构成进行调整，分年龄、社区进行推算，做X2检验，P＜0．05为差异有显著意义．不同胃疾病中Hp感染率及CagA+Hp感染率用百分数表示，做X2检验，P＜0．05为差异有显著意义。2结果2．1自然人群抗HpU-IgG及抗Hp-CagA-IgG感染与性别的关系城市和农村、男性和女性Hp感染率差异均尤显著意义(P＞0．05，表1)．2．2西安地区自然人群(0岁～60岁)Hp及CagA+ Hp感染率的分布西安地区农村及城市在0岁年龄段、1岁年龄段Hp感染率比较，差异分别有显著性意义(P＜0．05)；其他各年龄段Hp感染率及CagA感染率相比较，差异均无显著性意义(P＞0．05，表2，图1)．表1西安地区Hp感染率及CagA感染的的性别分布aP＞0．05vs农村组、女性组。2．3西安地区0岁～14岁儿童Hp及CagA+Hp感染率的分布西安地区农村及城市在0岁～2岁年龄段Hp感染率相比较，差异有显著意义(P＜0．01)，其他各年龄段Hp感染率及CagA感染率相比较，差异均无显著性意义(P＞0.05，表3，图2)．结果显示，西安地区Hp感染明显前移，2岁～3岁年龄段已达40％～50％。表2西安地区自然人群(0岁～60岁)Hp及CagA+Hp感染率的分布aP＜0．05，bp＞0．05vs城市组对应年龄段。表3西安地区O岁～14岁儿童Hp及CagA-Hp感染率的分布图1西安地区农村和城市Hp和cagA-Hp感染率。aP＜0．01，vs城市。图2西安地区0～14岁儿童Hp及CagA+Hp感染率的分布（农<