达能营养中心第二届学术研讨会论文集

江骥
北京协和医院

幽门螺杆菌(Helicobacter pylori)与幽门螺杆菌感染
不同国家幽门螺杆菌感染情况的概述
幽门螺杆菌感染的途径和饮食习惯
我国儿童幽门螺杆菌感染的初步调查
1 方法学:13C-尿素呼气试验(13C-urea Breath test)
  原理, 过程
2 初步流调和结果
  北京,山东,江苏,贵州,广东,西藏
3 幽门螺杆菌感染与胃癌的发生
4 父母幽门螺杆菌感染与儿童

摘要:
幽门螺杆菌研究概况
  1983年,澳大利亚学者Warren和Marshall报告,在人胃粘膜活检组织中分离这种细菌,即幽门螺杆菌(Helicobacter pylori, HP;原名幽门弯曲菌 Campylobacterpylori, CP) 并认为该菌可能是慢性胃炎和消化性溃疡的病原菌。随后各国学者相继进行了研究,短短几年内,大量的研究资料表明,HP是慢性胃炎的主要病因,在消化性溃疡,特别是十二指肠溃疡的发病中可能起重要作用,与非溃疡性消化不良和胃癌亦有一定关系,世界卫生组织认定,HP是导致胃癌的头号因素。
  国外的流行病调查结果提示,发展中国家比发达国家的感染率高,东方人感染率比西方人高,不少作者认为,这与东方人的饮食习惯有关(如共餐制,筷子等)。
  HP是一种微需氧的革兰氏阴性细菌,人的胃粘膜是HP的自然定植部位;另外,在Barrett食管,Meckel室和直肠的胃粘膜化生区也可检出HP。但在正常肠粘膜上皮未能检出HP定植。HP在电镜下是一个小杆菌,长约2-3mm,常有1-2弯曲呈S形或弧形,有鞭毛。
(三)HP的传染途径
  主要为人—人之间的传播,包括口—口传播和粪—口传播。
(四)HP的致病机理
  HP能导致疾病的主要原因在于:1)其能产生有害的酶,包括尿素酶;产生氨,氨是细胞毒素,可损害上皮屏障,破坏胃泌素/胃酸反馈体系 2)过氧化氢酶; 3)HP菌体本身就是一种内毒素,可以刺激免疫系统,引起炎症。
HP的诊断方法
  诊断HP感染的方法数种:其中包括细菌培养、病理学染色、快速尿素酶试验、血清免疫学检查和同位素呼气试验等。前三种方法均需通过胃镜来获取一定数量的组织标本,故而有一定的创伤和痛苦,此外,由于HP在胃中的生长呈斑块状分布,在通过胃镜活检时,即使事实上存在有HP的感染,但在取标本时也容易有漏诊的可能,特别是近年来有一些报道发现这种细菌存在于胃体部,而不仅仅在幽门部位。故而取标本的不足容易导致假阴性的结果发生。
细菌培养
活检组织尿素酶试验
组织切片染色
血清学


门螺杆菌感染与胃肠疾病关系的假说
13C尿素呼气试验
该方法采用了稳定同位素以及质谱学等技术,准确、特异、快捷。灵敏度和特异性都在95%左右,受检查者无痛苦,无创伤,无放射性损伤。
2.原理
由于HP具有内源性、特异性的尿素酶,可将尿素分解为NH3和CO2,CO2在小肠上端吸收后进入血液循环并随呼气排出。让受检查者口服13C标记的尿素后,如果胃中存在HP感染,就可以将13C标记的尿素分解为13C标记的CO2因此,通过用高精度的气体同位素比值质谱仪(Gas Isotopic Ratio Mass Spectrometer, GIRMS)来探测呼气中的13C—CO2即可诊断HP的感染,由于口服的13C-尿素到达胃后呈均匀分布,只要在13C-尿素接触的部位存在着HP感染,就可灵敏地检测到。
HP的流行病学
HP感染在世界各地都较为常见,有人估计约半数的人口其胃内有HP定居,人们已接受HP是慢性胃炎的主要病因。胃炎的发病率与HP的感染率均随年龄的增长而增高。一旦感染HP,多持续终生。在不同地区,不同种族,不同人群或同一人群的不同个体之间,HP的感染率差别很大,这与卫生习惯和设备有关。在经济不发达国家感染率较高,初次感染的年龄早,5岁儿童的感染率已达50%,成人感染率可达90%。在发达国家,HP的感染率与以往报道的慢性胃炎和消化不良新发病例的发病率大致相同,即随年龄每年增加1-2%,在不同信仰、种族、道德标准和社会经济地位人群间差别也显著。该菌的传播主要是人—人之间通过粪—口或口—口途径。已有报道在家庭内通过密切接触可造成传播。另外,内镜检查也可传播HP,具有活力的螺旋形HP在河水中至少可存活一周,而球形的HP则可存活一年多,但后者无致病力。HP的流行病学模式与甲型肝炎和疫苗预防问世前的脊髓灰质炎相似,后两种病均经粪—口途径传播,流行病学资料表明,胃粘膜病变与消化性溃疡和胃癌相关,初次感染HP年龄较早的人群,胃癌的发病率也高。北京协和医院和国内的有关单位合作,采用 13C-尿素呼气试验,对我国胃癌高发区和低发区部分正常儿童(3-12岁)的HP感染情况进行了调查,结果如表所示:
表 我国部分地区儿童螺杆菌感染的流行病学调查结果
地区
病例数
年龄(岁)
HP感染率
(%)
胃癌死亡率
(每十万人)
北京
84
3-12
32.18
9.86
临朐(山东)
98
3-12
69.39
38.00
从化(广东)
83
3-15
35.00
2.32
花溪(贵州)
119
3-12
12.61
6.93
扬中(江苏)
119
4-11
73.11
73.19
拉萨(西藏)
110
4-12
92.73
Helicobacter Pylori Infection and the Eating Habits of Chinese Children
Jiang Ji
Beijing Union Hospital
l        Helicobacter pylori and its infection
l        The overview of Helicobacter pylori infection in different countries
l        The ways of Helicobacter pylori infection and the eating habits
l        Preliminary survey of the Helicobacter pylori infection of children in China
 
1.  Method: 13C-urea Breath test
Principle, procedure
2.  Epidemiological study and result
Beijing, Shandong, Jiangsu, Guizhou, Guangdong, Tibet
3.  Helicobacter pylori infection and gastric carcinoma
4.  The Vertical transmission of Helicobacter pylori between parents and their children
 
Abstract:
 
Overview of research on H.P.
 
HP was separated from human gastric mucosa by Warren and Marshall in Australia in 1983. Extensive research studies have shown that HP is a chief etiological factor of chronic gastritis, and it may also play an essential role in the development of peptic ulcer, especially the duodenal ulcer. In addition, HP may associate with functional dyspepsia and gastric cancer. According to WHO, HP is the top-one etiological factor of gastric cancer. 
The results of epidemiological studies indicated that the prevalence of HP infection was higher in developing countries than developed countries. Eastern people had a higher rate of infection than their western counterparts, which may be related to the eating habits of eastern people (e.g. sharing food, using chopstick). 
HP is a gram-negative curved or spiral bacterium with a 2-6 Uni-polar sheathed flagella which is originally located in gastric epithelium (include the gastric mateplasiu in Barrett’s esophagus, Meckel’s diverticulum and rectum).  It can’t be separated from the normal intestinal epithelium.
 
3.        The transmission route of  HP infection
Several ways of transmission from person to person have been confirmed.  The predominant route of infection is considered to be vomit-oral in early life.  The oral-oral route and the fetal-oral sent are also considered to be possible.
 
4.        The pathogenic mechanism of HP infection
HP is able to colonize because of its adapted motility and its ability to form a neutral microenvironment with urease activity.  Adhesions permit adherence to surface cells of the gastric epithelium and damage may be caused by enzymes such as protease, catalase, and etc., on the cytotonic proteins Cag A or Vac A.

The diagnosis of HP infection

Non-endoscopic
Serology
13C urea breath test
Endoscopy
Biopsy urease test
Histology
Cell culture
 
 
Epidemiology of HP infection
 
The HP infection is very common worldwide. It is estimated that about half of the population has HP infection in their stomachs. It is believed that HP is the major risk factor for chronic gastritis. The older, the higher the incidence of chronic gastritis and the rate of HP infection. It will last for lifelong if it is infected. The infection rate varies significantly in different regions, races, and populations and between individuals which closely related to personal habit and sanitation equipment. It is more common in developing countries. The infection rate in children aged 5 years and in adults are 50% and 90% respectively. Epidemiological studies showed that the younger the HP infection, the higher the incidence of gastric cancer.
 
We conducted a survey of HP infection in children aged between 3-12 years in areas with high-prevalent and low-prevalent gastric cancer by using 13C-urea Breath Test.
 

Epidemiological Studies of HP infections in some areas of China

Areas
Cases
Age (y)
Prevalence of HP infection
Mortality gastric cancer
Beijing
84
3-12
32.18
9.86
Linqu(Shandong)
98
3-12
69.39
38.00
Conghua(Guangdong)
83
3-15
35.00
2.32
Huaxi(Guizhou)
119
3-12
12.61
6.93
Yangzhong(Jiangsu)
119
4-11
73.11
73.19
Lhasa(Tibet)
110
4-12
92.73