幽门螺杆菌 Open Access
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2004-05-15; 12(5): 1100-1103
在线出版日期: 2004-05-15. doi: 10.11569/wcjd.v12.i5.1100
胃食管反流病与幽门螺杆菌相关性胃炎及胃肠激素的关系
吴灵飞, 王炳周, 冯家琳, 郑宗茂, 张金池, 曾哲
吴灵飞, 王炳周, 郑宗茂, 曾哲, 汕头大学医学院第二附属医院消化科 广东省汕头市 515041
冯家琳, 汕头大学医学院第二附属医院信息科 广东省汕头市 515041
张金池, 汕头大学医学院第二附属医院放免室 广东省汕头市 515041
吴灵飞, 男, 1964-09-26生, 汉族, 湖北省武汉市人. 1986年湖北医科大学毕业, 医学硕士, 副主任医师. 主要从事胃肠疾病研究.
基金项目: 广东省中医药管理局资助项目, No. 99591.
通讯作者: 吴灵飞, 515041, 广东省汕头市东厦北路69号, 汕头大学医学院第二附属医院消化科. lingfeiwu@21cn.com
电话: 0754-8355461 传真: 0754-8346543
收稿日期: 2003-12-12
修回日期: 2004-01-09
接受日期: 2004-01-12
在线出版日期: 2004-05-15

目的: 通过对胃食管反流病(GERD)患者幽门螺杆菌(H. pylori)感染、H. pylori相关性胃炎的程度及血清胃泌素(Gas)、胃动素(Mot)水平的检测, 探讨H. pylori与GERD之间的关系.

方法: GERD患者53例按内镜表现分为非糜烂性反流病(NERD)和反流性食管炎(RE)2组, 结合病检评估胃窦、胃体黏膜炎症及食管黏膜损伤, 采用放免法检测空腹血Gas, Mot水平. H. pylori检测采用血清抗体法, 组织银染及尿素酶依赖试验(14C-尿素呼气试验或快速尿素酶试验), 三项试验中二项阳性定为H. pylori感染. 20名正常健康人作对照. 32例NERD患者18例H. pylori阳性, 14例阴性; 21例RE患者12例H. pylori阳性, 9例阴性. RE组Ⅰ级食管炎11例, Ⅱ级7例, Ⅲ级3例. 53例GERD中, H. pylori (+)30例, H. pylori(-)23例.

结果: RE组Mot水平显著低于对照组(360±126 vs 440±110 mg/L, aP<0.05). NERD组Mot水平与对照组相比差异无显著性(P>0.05). NERD和RE二组患者Gas水平与对照组相比均无显著性差异(P>0.05), H. pylori (+) GERD患者Gas水平显著高于对照组(35.8±11.6 vs 28.5±10.6 mg/L, bP<0.05). H. pylori (+) GERD患者与H. pylori (-)组相比, 胃窦胃炎及胃体胃炎均有高度显著性差异(P<0.005), 但2组食管炎程度并无显著性差异(P>0.05), 胃炎的程度与H. pylori感染有关但与食管炎的程度无关.

结论: Mot与RE发病有关. H. pylori (+)GERD患者有较高Gas水平及明显胃窦及胃体炎症, 但H. pylori性胃炎与食管病变分级无关.

关键词: N/A
引文著录: 吴灵飞, 王炳周, 冯家琳, 郑宗茂, 张金池, 曾哲. 胃食管反流病与幽门螺杆菌相关性胃炎及胃肠激素的关系. 世界华人消化杂志 2004; 12(5): 1100-1103
Relationship of Helicobacter pylori related gastritis, gut hormones and gastroesophageal reflux disease
Ling-Fei Wu, Bing-Zhou Wang, Jia-Lin Feng, Zong-Mao Zheng, Jin-Chi Zhang, Zeng Zhe
Ling-Fei Wu, Bing-Zhou Wang, Zong-Mao Zheng, Zeng Zhe, Department of Gsatroenterology; Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Jia-Lin Feng, Department of Information; Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Jin-Chi Zhang, Department of Radioimmunoassay, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Supported by: Guangdong Chinese Traditional Medicine Management Agency, No. 99591.
Correspondence to: Dr. Ling-Fei Wu, Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong Province, China. mailto:lingfeiwu@21cn.com
Received: December 12, 2003
Revised: January 9, 2004
Accepted: January 12, 2004
Published online: May 15, 2004

AIM: To evaluate the relationship of H. pylori infection, H. pylori -related gastritis, serum gastrin and motilin levels and esophageal lesions in gastroesophageal reflux disease (GERD).

METHODS: All 53 GERD patients were divided into non-erosive reflux disease (NERD group, 32 cases) and reflux esophagitis (RE group, 21 cases ) by endoscopy. The degrees of gastritis in antrum and body as well as esophagitis were evaluated by pathological examinations. Fasting serum gastrin and motilin concentrations were determined by radioimmunoassay. H. pyloriwas examined by serum H. pylori-antibody, Warthin-Starry stain, urease-dependent test (rapid urease test or 14C-breath test).H. pylori infection was affirmed when at least two of three tests were positive. 20 normal persons were as controls. In NERD group, 18 were H. pylori positive and 14 were negative. In RE group 12 were H. pylori positive and 9 were negative. According to the classification of esophagitis, 11 were ClassⅠ, 7 ClassⅡ and 3 Class Ⅲ. There were 30 H. pylori (+) and 23 H. pylori (-) in 53 GERD patients.

RESULTS: As compared with healthy controls, fasting serum motilin levels in RE group were significantly lower (360±126 vs 440±110 mg/L, aP < 0.05) and those in NERD group were similar (P > 0.05). No differences in gastrin levels were found between NERD or RE group and controls (both P > 0.05). The serum gastrin levels in H. pylori (+) GERD were significantly higher than controls (35.8±11.6 vs 28.5±10.6 mg/L, bP < 0.05). In H. pylori (+) GERD patients, gastritis grades in the antrum and gastric body were significantly higher than that in H. pylori (-) patients (χ2 = 32.97, χ2 = 15.67, both P < 0.005). The esophagitis grades were similar in H. pylori (+) and H. pylori (-) GERD (χ2 = 0.82, P > 0.05). The gastritis grades were not associated with the esophagitis degrees, but with H. pylori infection.

CONCLUSION: Motilin is involved in the pathogenesis of RE. H. pylori can lead to hypergastrinemia and gastritis in the antrum and gastric body.

Key Words: N/A
0 引言

胃食管反流病(gstroesophageal reflux disease, GERD)是一种临床常见疾病, 根据有无食管炎症状, 一般将之分为非糜烂性胃食管反流病(non-erosive reflux disease, NERD)、反流性食管炎(reflux esophagitis, RE)和Barrett食管三种类型[1], 其发病机制较复杂. 一般认为与食管下端扩约肌(LES)、膈肌功能异常[2-5]及酸突破[6-10]有关, 与幽门螺杆菌 (H. pylori)的关系争论颇多[11-17]. 我们通过观察NERD和RE患者血胃动素与胃泌素含量的变化, 并作H. pylori阳性和阴性GERD患者胃炎与食管炎程度的相关性分析, 旨在探讨H. pylori及其胃炎与GERD之间的关系.

1 材料和方法
1.1 材料

本院2001/10 -2003/10门诊患者具有反酸、烧心、反食、胸痛等症状至少3 mo. 内镜诊断为RE者应排除消化性溃疡及肿瘤. 内镜检查阴性者经质子泵抑制剂(PPI)试验 (Losec 20 mg bid ×7 d)明显减轻症状则诊断为NERD[18]. 由于Barrett食管仅3例, 故本组GERD剔除Barrett食管患者, 只包括NERD(n = 32)和RE (n = 21)二类患者. 所有患者均无上消化道手术史及严重心、肝、肾等疾病, 近1 mo均无使用非甾体类消炎药、胃肠动力药及抗H. pylori药物. 对诊断为NERD的患者回顾性分析PPI试验前的检测数据. 对照组20名健康志愿者, 均无GERD症状, 亦无近期服药史. RE分级参照2000全国《反流性食管病(炎)治疗及诊断方案(试行)》标准[19]. Ⅰ级: 食管黏膜点状或条状发红、糜烂, 无融合现象;Ⅱ级: 有条状发红, 糜烂, 并有融合, 但非全周性; Ⅲ级: 病变广泛、发红、糜烂, 融合呈全周性, 或有溃疡. 胃炎的诊断标准参照全国《慢性胃炎研讨会共识意见》标准[20], 分别按部位(胃窦、胃体及胃底贲门部)各取活检组织行HE染色及病理学检查, 根据炎症的程度分为无、轻度、中度及重度四级.

1.2 方法

采用WS染色、尿素酶依赖试验(快速尿素酶试验或14C-呼气试验)及查血清H. pylori抗体的方法, 三项试验中二项阳性诊断H. pylori感染. 所有病例均于清晨空腹静脉采血, 按照说明书以放免法进行检测. Gas 试剂盒购自北方生物技术研究所, Mot试剂盒购自301医院科技开发中心放免所.

统计学处理 计量资料采用mean±SD表示, 均数的检验采用t检验. 计数资料采用χ2检验或Radit分析, P<0.05认为差异有统计学意义.

2 结果

NERD组32例, 男19例, 女13例, 平均年龄43±11岁, 其中H. pylori (+)18例, H. pylori (-)14例. RE组21例, 男14例, 女7例, 平均年龄47±12岁, 其中H. pylori (+)12例, H. pylori (-)9例. 内镜分级:Ⅰ级11例, Ⅱ级7例, Ⅲ级3例. 二组患者H. pylori感染率均为56%, 无统计学差异(P>0.05). 二组年龄亦无显著性差异(P>0.05). 对照组20例, 男12例, 女9例, 平均年龄35±12岁, 胃镜检查阴性.

2.1 血清Gas、Mot水平

GERD患者根据内镜下表现分为阴性(NERD)和阳性(RE)2组. 2组患者血Gas水平与对照组比较均无显著性差异(P>0.05). NERD组Mot水平较低, 但与对照组比较无统计学意义(P>0.05). RE组Mot含量与对照组相比, 有显著性差异(aP<0.05). 若根据H. pylori情况分组, H. pylori(+)组(n = 30)GERD患者Gas水平较高, 与对照组相比有显著性差异(bP<0.05), H. pylori(-)组(n = 23) GERD患者Gas水平与对照组相比无显著性差异(P>0.05). H. pylori (+)/(-)组Mot水平均低于对照组, 但无统计学意义(P>0.05, 表1).

表1 GERD患者血清Gas, Mot含量 (mean±SD, mg/L).
分组nGasMot
内镜表现 NERD3232.9±12.1405±113
RE2126.8±9.8360±126a
H. pylori (+)3035.8±11.6b378±10
(-)2323.5±10.7300±121
对照组2028.5±10.6440±110a
aP<0.05, t = 2.16 vs对照组;
bP<0.05, t = 2.26 vs对照组.
2.2 H. pylori (+)/(-) GERD患者胃食管炎

H. pylori (+)胃窦胃炎、胃体胃炎均较明显. 30例H. pylori (+)患者中有19例有轻度胃窦部炎症, 8例中度炎症, 3例重度炎症. 在胃体部炎症中, 18例为轻度炎症, 5例为中度炎症, 4例重度炎症. 23例H. pylori(-)患者中胃炎均较少见. H. pylori (+)/(-)组比较, 胃窦胃炎及胃体胃炎均有高度显著性差异(P<0.005). 二组患者食管炎程度的比较则无显著性差异(P>0.05, 表2). 胃窦炎症、胃体炎症的程度与食管病变的程度进行Radit分析, 均未见显著性差异(P>0.05). GERD患者食管病变的程度均不与胃窦、胃体炎症程度相关.

表2 GERD患者H. pylori(+)/(-)组胃食管炎症分级 (n).
H. pylorin胃窦胃炎
胃体胃炎
食管炎
无轻中重无轻中重无轻中重
(+)30019833185418741
(-)23174201452214432
χ2 = 32.97χ2 = 15.67χ2 = 0.82
P<0.005P<0.005P>0.05
3 讨论

GERD的发生与多因素有关. 食管胃动力异常、食管对反流物清除机制缺陷或黏膜上皮防御机制损伤均可导致GERD发病[20-24]. 然而, 影响LES压力及食管蠕动的因素颇多[2-5]. 研究表明, Mot水平降低可使胃排空延缓[24-27], Gas则可使LES压力升高, 但生理状态下Gas对LES的影响并不大[27]. 文献报道H. pylori 感染者常引起高Gas血症, 根除H. pylori后可使Gas水平恢复正常[24,28]. H. pylori (+)GERD 患者是否亦有Gas异常未见报道. 本组中, H. pylori (+)组Gas水平显著高于H. pylori(-)组, 说明H. pylori同样对GERD患者Gas有影响. Gisbert et al[28]对H. pylori(+)与H. pylori(-)GERD患者进行食管测压及24 h食管pH值测定, 结果二组患者并无显著性差别. 本组中 , GERD患者无论有无食管黏膜的损伤, 其空腹血中Gas水平与对照组相比均无统计学意义. H. pylori(+)GERD患者 Gas较高但与Mot无相关, 表明在GERD的发生过程中Gas对食管动力并未起重要作用. RE组Mot显著性低于正常值, 表明Mot与GERD进展有关. GERD与H. pylori的关系一直引人注目. 流行病学资料表明, GERD患者H. pylori感染率低. 士耳其后裔的人群中H. pylori感染率高(60.6%)而RE发生率低(9.7%), 荷兰人群中H. pylori感染率低(18.5%)而RE发生率高(33.0%), 二者呈反比关系[29-30]. 但是, 不同地区有不同的结果[31-35]. 在本组中, GERD主要为NERD及RE患者, Barrett食管少见, 且二组H. pylori感染率及年龄均无显著性差异, 说明H. pylori及年龄因素在GERD病变逐渐进展的过程中并不起作用. 我们认为GERD患者的这些特点可能与我国为H. pylori高发区及种族差异有关 .

本组患者H. pylori感染与GERD食管炎病变程度无关, 但与胃窦胃炎及胃体胃炎均有关. 在21例RE患者中, 11例H. pylori(+)且病变程度较轻. 而在24例H. pylori(+)患者中, 均有胃窦部炎症, 部分患者胃体部炎症更为严重. 由于本组无近期服药病史, 胃部炎症主要应为H. pylori相关性胃炎[35], 但胃炎与食管黏膜损伤无关. 有学者认为不是H. pylori而是胃炎对GERD 有保护作用[10,36-39]. 我们认为这应依具体情况而定. 本组患者中胃体胃炎较重者食管病变较轻, 而胃体炎症较轻者GERD症状常较明显, 其他学者亦观察到类似现象[16,21]. 此外, 我们注意到RE患者内镜下贲门炎不多见. 21例RE中仅6例出现贲门炎, 为28.6%. 32例NERD患者中, 只2例(6.2%)有贲门炎, 并未见Csendes et al报道GERD患者贲门肠上皮化生多见的情况[40]. 这些结果的差异可能与不同人群的遗传背景、H. pylori菌株的生物学特性、个体食管病前状态及对疾病的不同反应性有关[10-12,41-47].

本项研究中, NERD的诊断是采用PPI试验和非24 h食管pH值检测金标准, 毕竟pH检测、压力测定及核素法条件要求较高或患者依从性差, 难于普及. 文献报道, PPI试验敏感性和特异性可达80%以上[18]. 我们认为对疑似NERD的病例采用此法方便简捷, 值得推广. 然而, 亦应注意到PPI对酸耐受力差, 在胃中暴露于酸后易失效, 因此对某些胃排空延缓的病例由于药物可能已在胃中失效或减效并未显出实际效果, 因此本组应除外PPI无效的GERD病例. 此外, 胆汁反流的病例亦不在此列. 寻找一种简便有效的诊断方法或筛选指标有助于更广泛地探讨GERD的发病机制[48].

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