临床研究 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-11-15; 11(11): 1715-1719
在线出版日期: 2003-11-15. doi: 10.11569/wcjd.v11.i11.1715
功能性消化不良患者症状分型、胃排空功能、胃肠激素水平的相关性
唐红卫, 黄裕新, 徐海峰, 高巍, 周润锁, 尚磊, 王庆莉, 高峰, 安晓丽
唐红卫, 黄裕新, 高巍, 王庆莉, 中国人民解放军第四军医大学唐都医院消化内科 陕西省西安市 710038
唐红卫, 中国人民武装警察部队总医院消化内科 北京市 100039
唐红卫, 男, 1966-11-26 生, 北京人, 汉族. 1991年第四军医大学本科毕业, 2002年第四军医大学硕士毕业, 主要从事功能性消化不良研究.
徐海峰, 周润锁, 高峰, 安晓丽, 中国人民解放军第四军医大学唐都医院核医学科 陕西省西安市 710038
尚磊, 中国人民解放军第四军医大学预防医学系卫生统计学教研室 陕西省西安市 710033
通讯作者: 黄裕新, 710038, 陕西省西安市新寺路, 中国人民解放军第四军医大学唐都医院消化内科. tanghw@fmmu.edu.cn
电话: 029-3377421 传真: 029-3377721
收稿日期: 2003-03-21
修回日期: 2003-04-20
接受日期: 2003-05-24
在线出版日期: 2003-11-15

目的

通过放射性核素胃排空检测及血中胃肠激素检测, 了解功能性消化不良(functional dyspepsia, FD)患者症状分型、胃排空和胃肠激素的相互关系, 探讨其发病机制.

方法

以FD患者为观察对象, 依据罗马II标准, 将符合纳入标准的患者分为三个临床亚型, 每型患者随机取10人为一组, 并以10名健康志愿者作为对照组, 同步观察胃排空及相关胃肠激素的变化. 胃排空检测后, 再将30例FD患者分为2组, 胃排空正常组和胃排空延迟组. 通过99mTc标记的固体餐检测胃排空, 应用放射免疫法测定外周血中胃动素(motilin, MTL), 生长抑素(somatostatin, SS), P物质(substance P, SP)的含量. 应用硝酸还原酶法测定外周血中一氧化氮(nitric oxide, NO)的含量.

结果

溃疡样型组40%胃排空延缓, 胃半排空时间(GET1/2)及各时间段胃排空率(GE%)与健康对照组比较无显著差异(P>0.05), 与动力障碍样型组、非特异性型组比较亦无显著差异(P>0.05); 外周血SS升高(P<0.05), MTL, SP, NO与健康对照组比较无显著性差异(P>0.05). 动力障碍样型组70%胃排空延缓, GET1/2延长(P<0.05), GE% 15 min, 30 min与健康对照组比较差别不显著(P>0.05), 45 min及45 min以后各时间段减低(45 min, P<0.05; 60 min, P<0.05; 90 min, P<0.01; 120 min, P<0.01); 外周血SS升高(P<0.05), MTL、SP、NO与健康对照组比较无显著性差异(P>0.05).非特异性型组70%胃排空延缓, GET1/2延长(P<0.05), GE% 15 min、30 min与健康对照组比较差别不显著(P>0.05), 45 min及45 min以后各时间段减低(45 min, P<0.05; 60 min, P<0.05; 90 min, P<0.01; 120 min, P<0.01); 外周血SS升高(P<0.05), MTL, SP, NO与健康对照组比较无显著性差异(P>0.05). FD胃排空正常组与健康对照组比较外周血SS升高(P<0.05), MTL, SP, NO无显著性差异(P>0.05).FD胃排空延迟组与健康对照组比较外周血SS, NO升高(P<0.05), MTL降低(P<0.05), SP无显著性差异(P>0.05).

结论

FD患者有明显的胃动力障碍, 以动力障碍样型和非特异型为明显, 各亚型间存在不同发病机制, 症状分型有利于经验性治疗, 对FD患者进一步行胃排空检测, 有利于明确胃排空情况, 为治疗提供可靠依据.外周血MTL降低、NO含量升高与FD患者胃排空延迟有关.SS, SP与FD的关系有待进一步研究.

关键词: N/A

引文著录: 唐红卫, 黄裕新, 徐海峰, 高巍, 周润锁, 尚磊, 王庆莉, 高峰, 安晓丽. 功能性消化不良患者症状分型、胃排空功能、胃肠激素水平的相关性. 世界华人消化杂志 2003; 11(11): 1715-1719
Relationships among symptom sub-groups, gastric emptying and blood gut hormones in patients with functional dyspepsia
Hong-Wei Tang, Yu-Xin Huang, Hai-Feng Xu, Wei Gao, Run-Suo Zhou, Lei Shang, Qing-Li Wang, Feng Gao, Xiao-Li An
Hong-Wei Tang, Yu-Xin Huang, Wei Gao, Qing-Li Wang, Department of Gastroenterology, Tangdu Hospital, Xi'an 710038, Shaanxi Province, China
Hong-Wei Tang, Department of Gastroenterology, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China
Hai-Feng Xu, Run-Suo Zhou, Feng Gao, Xiao-Li An, Department of Nuclear Medicine, Tangdu Hospital, Xi'an 710038, Shaanxi Province, China
Lei Shang, Department of Health Statistics, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an 710033, Shaanxi Province, China
Corresponding author: Dr. Yu-Xin Huang, Department of Gastroenterology, Tangdu Hospital, Xi'an 710038, Shaanxi Province, China. tanghw@fmmu.edu.cn
Received: March 21, 2003
Revised: April 20, 2003
Accepted: May 24, 2003
Published online: November 15, 2003

AIM

To study the relationships among symptom subgroups, gastric emptying and gastrointestinal hormones in patients with functional dyspepsia (FD) and to explore pathogenesis of FD.

METHODS

The patients with FD were divided into 3 subgroups according to the RomeIIcriteria and 10 cases were selected randomly from each subgroup. Ten healthy subjects served as control. Thus 4 subgroups were set up, including the ulcer-like dyspepsia group (10 cases), the dysmotility-like dyspepsia group (10 cases), the unspecified dyspepsia group (10 cases) and the control group (10 healthy subjects). Changes of radionuclide gastric emptying and blood levels of relevant gastrointestinal hormones were observed synchronously. After gastric emptying was measured, the 30 cases of FD were divided into 2 groups: the normal gastric emptying group and the delayed gastric emptying group. Gastric emptying was recorded by 99mTc-labelled solid food. Changes in motilin(MTL), somatostatin(SS), substance P(SP)and nitric oxide(NO)contents in peripheral blood were determined by radioimmunoassay and nitrate reductase technique.

RESULTS

In the ulcer-like group, 40% patients had gastric emptying delay while the half gastric emptying time (GET1/2) and gastric emptying rate (GE%)at every time-point did not show significant changes(P<0.05)compared with control group and the other two subgroups of FD. The levels of SS in peripheral blood were increased significantly (P<0.05). However, the levels of MTL, SP, NO did not show significant changes (P<0.05) compared with control group. In the dysmotility-like group, 70% patients had gastric emptying delay, meanwhile, GET1/2 was prolonged significantly (P<0.05), and GE% was decreased significantly (15 min, P>0.05; 30 min, P>0.05; 45 min, P<0.05; 60 min, P<0.05; 90 min, P<0.01; and 120 min, P<0.01, respectively). Levels of SS in peripheral blood were increased significantly (P<0.05), whereas levels of MTL, SP, NO did not show significant changes (P>0.05). In the unspecified group, 70% of patients had gastric emptying delay, meanwhile, GET1/2 was prolonged significantly (P<0.05), and GE% was decreased significantly (15 min P>0.05; 30 min, P>0.05; 45 min, P<0.05; 60 min, P<0.05; 90 min, P<0.01; and 120 min, P<0.01, respectively). Levels of SS in peripheral blood were increased significantly (P<0.05), whereas levels of MTL, SP, NO did not show significant changes (P>0.05). In the normal gastric emptying group of FD, levels of SS in peripheral blood were increased significantly (P<0.05), whereas levels of MTL, SP, NO did not show significant changes (P>0.05). In the delayed gastric emptying group of FD, levels of SS and NO in peripheral blood were increased significantly (P<0.05), whereas levels of MTL were decreased significantly (P<0.05), meanwhile, levels of SP did not show significant changes (P>0.05).

CONCLUSION

Gastric motility disturbance plays an important role in pathogenesis of dysmotility-like dyspepsia and unspecified dyspepsia. Three subgroups of FD have different mechanisms and the Rome II criteria have practical importance in diagnosis and therapy of FD. Therefore, gastric emptying test has significance in evaluation of gastric motility function and in the treatment of FD. The increase of NO and the decrease of MTL are related to gastric emptying delay. The roles of SS and SP need to be studied further.

Key Words: N/A


0 引言

功能性消化不良(functional dyspepsia, FD)是一常见的征侯群, 占消化疾病患者的20-40%, 对患者的生活质量有明显影响[1,2], 因此一直是人们研究的热点问题.新近发表的功能性胃肠道紊乱的罗马II分类体系是以症状为基础的诊断标准[3,4]. 根据罗马II分类体系标准[5-7], FD的诊断标准为在过去的12 mo里, 有顽固的反复发作的上腹部正中疼痛不适, 这些症状至少持续12 wk, 但不一定连续(例如1wk内仅1 d); 通过内镜证实没有明显的器质性疾病可以解释症状; 也没有明显的迹象表明, 消化不良可以通过排便缓解或同大便的频度或形状的变化有关. 该标准还将FD存在的主要症状分为3种亚型: (1)溃疡样消化不良型: 以集中在上腹部的疼痛为主要症状; (2)动力障碍样消化不良型: 以集中在上腹部的非疼痛性不适为主要症状, 包括上腹部饱胀感、早饱、恶心; (3)非特异性消化不良型, 症状不典型, 不完全符合溃疡样或动力障碍样的标准. 而将烧心、反酸为主的症状列入胃食管反流性疾病中. 然而, FD发病机制目前尚未明确, 我们依据罗马II标准测定FD患者胃排空功能及胃肠激素水平并探讨其发病机制及临床意义.

1 材料和方法
1.1 材料

从依次连续就诊的本院门诊及住院患者中随机选取符合罗马II标准的FD患者30例, 每个临床亚型10例, 男7例, 女23例, 年龄19-60岁(平均38岁), 病程1-15 a; 挑选健康志愿者10名(男5名, 女5名), 年龄19-53岁(平均40岁). 胃排空检测后, 将患者再分为胃排空延迟组和胃排空正常组. SPECT(单光子发射计算机断层照相机)为法国Sophycamera公司生产的DS7型.胃动素(motilin, MTL) 试剂盒为北京东雅生物技术研究所提供, P物质(substance P, SP)和生长抑素(somatostatin, SS)试剂盒为北京海科锐生物技术中心提供, 一氧化氮(nitric oxide, NO)试剂盒为南京建成生物工程研究所提供.

1.2 方法

1.2.1 胃排空检测 受检者均于检查前1 d夜间及检查当日晨禁饮食12 h, 2 wk内未服用任何影响胃肠运动的药物, 如吗丁啉、西沙必利、阿托品等.将37MBq99mTc淋洗液加至植酸钠药瓶中, 5 min后取出药液测定其放射性浓度, 准确无误后标记在一个油煎鸡蛋上. 试餐成分包括99mTc植酸钠胶体37MBq, 油煎鸡蛋一个(50 g), 面包100 g, 植物油20 g, 总热卡为1.531 MJ (366 kCal).进餐于5 min内完成, 受检者食入试餐后, 即取仰卧位, 将装有低能通用型准直器的SPECT探头视野中心置于受检者上腹部, 将全胃作为"感兴趣区", 采集放射性计数并显像共60 s, 作为患者进食的总放射性.此后分别于15、30、45、60、90、120 min时采像.然后, 描画胃感兴趣区(region of interest, ROI), 数据传入计算机, 经专用计算机软件处理, 绘制试餐后"时间-胃排空率"曲线, 据此计算胃半排空时间(gastric half emptying time, GET1/2)、各时间点胃排空率GE (%).按下式分别计算各时段胃排空率: GE(%) = (Cmax-Ct / K)/ Cmax ×100%, Cmax为胃区最大放射性计数, Ct为时间t时胃内放射性计数, K为时间t 时的衰变率. 检测期间室内恒温恒湿, 患者在采像间隙可在室内自由走动.

1.2.2 胃肠激素检测 禁饮食12 h后, 于清晨8: 00时胃排空检测前, 在肘静脉抽取血样5 mL, 其中4 mL静脉血置于4 °C预冷的试管内, 每个试管含100 g/L EDTA-Na2 100 μL及抑肽酶2 000 kU (500 MU/L), 用于MTL, SP, SS检测. 另外1 mL静脉血直接置于4 °C预冷的试管内, 用于NO检测. 4 °C 3500 r/min离心15 min, 分离血浆、血清于-70 °C保存待测. 采用放射免疫法测定MTL, SP, SS. 采用硝酸还原酶法测定NO. 按说明严格操作.

统计学处理 数据以标准差mean加减SD表示, 两均数的比较采用t检验, 两定量资料间呈线性关系者采用直线相关分析, 两定量资料间呈非线性关系者采用曲线拟合并进行拟合优度检验, 所有结果均由SPLM统计专业软件自动得出.

2 结果
2.1 FD患者胃排空

溃疡样型FD患者胃半排空时间(GET1/2)、各时间段胃排空率(GE%)与健康对照组比较无显著差别(P>0.05), 与动力障碍样型组、非特异性型组比较亦无显著差别(P>0.05); 动力障碍样型和非特异性型FD患者GET1/2延长, 15、30 min GE%与健康对照组比较差别不显著(P>0.05); 45 min及45 min以后各时间段GE%与健康对照组比较降低(45 min P<0.05; 60 min P<0.05; 90 min P<0.01; 120 min P<0.01); 根据各组各时间段GE% 所绘制的拟合曲线显示: 溃疡样型组接近正常, 动力障碍样型组和非特异性型组属于缓慢排空型; 动力障碍样型组和非特异性型组虽然无明显差异, 但是二者胃排空曲线并不平行, 后者与前者比较胃排空先快后慢, 并且有1例患者存在十二指肠胃反流现象; 以正常人GET1/2时间为参考, 30例FD患者中, 胃排空延缓18例, 占60%, 其中, 溃疡样型4例, 动力障碍样型7例, 非特异性型7例(表1).

表1 各型FD患者胃半排空时间及不同时间段的胃排空率(n =10, mean±SD).
分组GET1/2(min)胃排空率/%
15 min30 min45 min60 min90 min120 min
健康对照组61±93.5±2.019.9±3.233.8±6.156.3±6.275.4±8.487.0±10.3
溃疡样型组73±202.5±2.117.3±3.229.5±5.041.8±10.162.8±10.275.6±11.1
动力障碍样型组87±28 a1.0±0.68.9±5.018.4±6.9a23.9±11.0 a43.8±10.7 b63.0±11.5b
非特异性型组89±26a1.7±0.910.9±5.812.3±9.3a20.6±11.6 a37.0±13.1 b57.7±15.5b

FD患者胃排空率与时间的回归方程: 对照组Y = 0.7 994t-1.6 971, R2 = 0.9 668, P<0.01; 溃疡样型组 Y = 0.6 815t-2.2 662, R2= 0.9 849, P<0.01; 动力障碍样型组 Y = 0.55t-5.71, R2 = 0.9 812, P<0.01; 非特异性组Y = 0.4 828t-4.8 024, R2 = 0.9 678, P<0.01.

2.2 胃肠激素检测结果

各型FD患者外周血SS升高(P<0.05), 而MTL降低, 但无统计学差异(P>0.05), SP, NO与健康对照组比较无显著性差异(P>0.05); FD患者各型组间相互比较外周血MTL, SP, SS, NO无显著性差异(P>0.05, 表2).

表2 各型FD患者外周血MTL, SS, SP, NO含量的变化(n = 10, mean±SD).
分组MTL (ng/L)SS (ng/L)SP (ng/L)NO (μmol/L)
健康对照组457±13222±1232±1739±26
溃疡样型组349±19564±34a33±1945±36
动力障碍样型组288±18268±33a37±1650±36
非特异性型组317±20785±61a35±1452±27
2.3 胃排空与胃肠激素的关系

FD胃排空延迟组外周血MTL降低(P<0.05), SS, NO升高(P<0.05), SP与健康对照组比较无显著性差异(P>0.05); FD胃排空正常组外周血SS升高(P<0.05), MTL, SP, NO与健康对照组比较无显著性差异(P>0.05); FD患者胃排空延迟组与胃排空正常组比较, 外周血MTL降低(P<0.05), NO升高(P<0.05), SS, SP无显著性差异(P>0.05, 表3).

表3 FD患者外周血MTL, SS, SP, NO含量的变化(mean±SD).
分组nMTL (ng/L )SS (ng/L)SP (ng/L)NO (μmol/L)
健康对照组10457±13222±1232±1739±26
胃排空正常组12509±15573±43a33±1929±18
胃排空延迟组18190±54ab72 ±46a37±1463±33ab
3 讨论

FD是一常见的临床征侯群, 占消化疾病患者的20-40%, 对患者的生活质量有明显影响, 因此一直是人们研究的热点问题. FD发病机制目前尚未明确, 可能涉及多种因素[8-14]. 多数学者认为胃肠运动功能障碍是FD的主要发病机制[15,16]. 研究表明30-80%的患者有胃排空延缓, 表现为胃液体和固体或混合餐排空延缓, 多数学者认为固体排空延缓较液体排空延缓常见. 促动力药能促进胃排空和改善消化不良症状, 进一步证明胃肠运动功能障碍是FD的主要病理生理机制[17-19]. 我们研究显示, 30例FD患者中, 胃排空延缓18例, 占60%.其中, 溃疡样型4例, 动力障碍样型7例, 非特异性型7例.提示FD患者有明显胃动力障碍, 主要表现为固体食物排空延迟, 从而证实了胃排空延缓是FD的重要病理生理机制. 并且胃排空延缓与症状无相关性[20,21].我们的研究还发现, 根据各组各时间段GE%所绘制的拟合曲线显示: 溃疡样型组接近正常, 动力障碍样型组和非特异性型组属于缓慢排空型; 以上结果表明FD患者存在胃固体食物排空延缓, 以动力障碍样型组和非特异性型组为明显, 而溃疡样型组虽然40%患者存在胃排空延缓, 但是与健康对照组比较差别不显著. 同时我们还发现, 动力障碍样型组和非特异性型组虽然无明显差异, 但是二者胃排空曲线并不平行, 后者与前者比较胃排空先快后慢, 并且有1例患者存在十二指肠胃反流现象, 表现为胃排空曲线60 min时出现第二波谷. 结果提示, FD三个临床亚型存在不同发病机制. 因此我们认为, 症状分型对FD患者起到初步筛选的作用, 有利于经验性治疗. 目前认为放射性同位素法是测定胃排空的"金标准"[22] , 对FD患者进一步行胃排空检测, 有利于明确胃排空情况, 为治疗提供可靠依据.

胃肠激素是胃肠运动功能的重要调节因素, 尽管许多胃肠激素生理作用已经明确, 但胃肠激素与动力障碍性疾病的关系尚未完全阐明. 研究发现FD患者多有胃排空延缓, MMCIII期减少、缺失, 同时各时相血中胃动素(MTL)浓度均低于正常, 缺乏MTL分泌高峰[23-26].进一步研究证实, FD患者血中NO水平升高, 抑制胃排空[27-29]. 我们的研究发现, 各型FD患者外周血MTL、NO与健康对照组比较无显著性差异, 而胃排空延迟组外周血MTL降低, NO升高, 提示MTL、NO外周血含量变化与FD患者胃排空延迟关系密切. 有研究[7]表明FD患者的症状、心理状况与血浆生长抑素(SS)含量明显相关. 我们的研究证实, FD患者空腹血浆SS明显高于健康人. 提示SS升高与FD发病相关, 其机制及作用有待进一步探讨. P物质(SP)与FD之间的关系尚不清楚[30,31]. 我们的研究证实FD患者空腹血浆SP含量无显著性变化, 但胃肠激素的作用方式有: (1)作为肽能神经递质; (2)直接与相应受体结合发挥效应; (3)调节其他神经递质释放和传递; (4)通过迷走神经介导, 在中枢和外周水平上对胃运动和胃排空进行精细的调节[32].因此SP与FD的关系有待进一步研究.

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