第11章 螺杆菌属

Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16;1(8390):1311-5. Abstract Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.
HP可通过多种细菌的黏附、毒力因子对黏膜细胞的
直接损伤，以及机体对细菌的免疫反应而导致的免
疫和（或）炎症性组织损伤等机制而引起消化性溃
疡、慢性胃炎、胃癌、胃MALT淋巴瘤的发生。
The Nobel Prize in Physiology or Medicine for 2005 jointly to Barry J. Marshall and J. Robin Warren for their discovery of
Most Helicobacter pylori strains that cause disease contain the cag pathogenicity island (PAI), a chromosomal region comprising approximately 37,000 base pairs and 29 genes Helicobacter pylori evolution and phenotypic diversification in a changing host Sebastian Suerbaum & Christine Josenhans Nature Reviews Microbiology 5, 441-452 (June 2007)
生物学形状
G— ，菌体弯曲呈螺旋型、S形、海鸥形，有鞭 毛（从毛菌）； 微需氧， 营养要求高，生化反应不活跃，但尿 素酶丰富——快速脲酶实验强阳性（主要鉴定 依据）。
Warthin-Starry's silver stain
致病性与免疫性
慢性胃炎
胃溃疡
胃癌
本菌检出率很高
胃黏膜相关B细胞淋巴瘤
Baidu Nhomakorabea
致病物质
• 侵袭因子：尿素酶、鞭毛和菌毛。 • 毒素：
– 空泡毒素（vacuolating toxin A,Vac A) – 细胞毒素相关蛋白（cytotoxinassociated gene-A，
Cag A ）
• 胞外酶：磷脂酶、触酶。
CagY (HP0527), a protein that probably forms a sheath covering the type IV pilus, CagC (HP0546), the putative cag pilin, and the translocated effector CagA (HP0547).
any symptoms related to the infection. • H. pylori causes chronic active, chronic persistent, and
atrophic gastritis in adults and children.
• Infection with H. pylori also causes duodenal and gastric ulcers. • Infected persons have a 2- to 6-fold increased risk of developing gastric cancer and mucosal-associatedlymphoid-type (MALT) lymphoma compared with their uninfected counterparts. • The role of H. pylori in non-ulcer dyspepsia remains unclear.
Helicobacter exploits integrin for type IV secretion and kinase activation Terry Kwok, Dana Zabler, Sylwia Urman, Manfred Rohde, Roland Hartig, Silja Wessler, Rolf Misselwitz, Jürgen Berger, Norbert Sewald, Wolfgang König & Steffen Backert Nature 449, 862-866(18 October 2007)
Species H. acinonychis H. anseris H. aurati H. baculiformis H. bilis H. bizzozeronii H. brantae H. canadensis H. canis H. cetorum H. cholecystus H. cinaedi H. cynogastricus H. equorum H. felis H. mustelae H. pametensis H. pullorum H. pylori
H pylori virulence factors
Helicobacter pylori phase variation suppresses development of TH cells into TH1 cells and could facilitate persistent colonization.
第十一章 螺杆菌属
（Helicobacter）
Scientific classification
Kingdom:
Phylum: Class: Order: Family: Genus:
Bacteria
Proteobacteria Epsilonproteobacteria Campylobacterales Helicobacteraceae Helicobacter
发病机制
1. 基因学说 HP基因多态性是造成HP感染后不同临床结局 主要的原因。空泡毒素A（VacA）基因和细胞 毒相关基因（CagA）及其基因表达的蛋白质 与致病有关。 2. 漏屋学说（Leak Roof Hypothesis） HP产生的尿素酶、过氧化物酶、脂酶等及其 产物氨、羟氨以及细胞毒素等，可损伤胃黏膜， 主要损伤胃窦部黏膜，受损伤的细胞表面pH升 高，从而阻滞氢离子由黏膜向胃腔内分泌，并 促使氢离子逆向扩散，进一步破坏了胃黏膜屏 障。
• 螺杆菌属（Helicobacter）是一群氧化酶和触 酶阳性、微需氧、37℃能够生长、在25℃和 42℃均生长不良的革兰阴性弯曲菌。
• 1989年Goodwin根据其超微结构、酶活性、 脂肪酸序列、生长特性等的不同，建议将其从 弯曲菌属中划分出来而成立一个新的属螺杆菌 属。 • 本属中现已鉴定的有19个种，研究得最多、最 常见的是幽门螺杆菌（H. pylori，Hp）。
Lancet. 1988 Dec 24-31;2(8626-8627):1437-42. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Marshall BJ, Goodwin CS, Warren JR, Murray R, Blincow ED, Blackbourn SJ, Phillips M, Waters TE, Sanderson CR. Source Department of Gastroenterology, Royal Perth Hospital, Western Australia. Abstract 100 consecutive patients with both duodenal ulcer and Campylobacter pylori infection were followed up to see whether eradication of C pylori affected ulcer healing or relapse. Patients were randomly assigned to 8 weeks of treatment with cimetidine or colloidal bismuth subcitrate (CBS), with tinidazole or placebo being given concurrently from days 1 to 10, inclusive. Endoscopy, biopsy, and culture were done at entry, in weeks 10, 22, 34, and 62, and whenever symptoms recurred. There was no maintenance therapy. C pylori persisted in all of the cimetidine-treated patients and in 95% of those treated with cimetidine/tinidazole, but was eradicated in 27% of the CBS/placebo group and 70% of the CBS/tinidazole group. When C pylori persisted, 61% of duodenal ulcers healed and 84% relapsed. When C pylori was cleared 92% of ulcers healed (p less than 0.001) and only 21% relapsed during the 12 month followup period (p less than 0.0001).
3. 促胃液素联系学说（Gastrin Link Hypothesis）
研究发现HP阳性的慢性胃炎及十二指肠溃疡患者的
血清促胃液素水平较HP阴性的患者高，清除HP可
使其血清促胃液素下降，认为氨-促胃液素-酸系统是 HP使胃内促胃液素-酸正常负反馈机制失衡，从而造 成胃黏膜损伤及十二指溃疡形成的原因。 4. 免疫学说
‘the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease’
Illnesses caused by H. pylori
• Most persons who are infected with H. pylori never suffer