修回日期: 2016-04-27
接受日期: 2016-05-09
在线出版日期: 2016-06-08
目的: 探讨血浆脑肠肽、中医证型与胃食管反流病(gastroesophageal reflux disease, GERD)病程之间的关系.
方法: 本文研究以178例GERD患者为研究对象, 分为5个证型: 肝胃郁热证、痰气交阻证、痰瘀互结证、中虚气逆证、气滞血瘀证, 同时应用酶联免疫吸附法随机对部分入组患者进行血浆生长抑素、5-羟色胺、血管活性肠肽、内皮素、促胃动素水平检测.
结果: 178例GERD患者中, 非糜烂性反流病(nonerosive reflux disease, NERD)组及反流性食管炎(reflux esophagitis, RE)组间比较, RE组肝胃郁热证较NERD明显升高, 差异有统计学意义(P<0.05), NERD组中虚气逆证、痰瘀互结证较RE组明显升高, 差异有统计学意义(P<0.05). 不同中西医证型与病程有关: 178例GERD患者中, 病程不足1年患者73例(41%), 病程1-5年患者72例(40.5%), 病程超过5年患者33例(18.5%). 其中NERD组病程超过5年的患者明显比RE组高; 肝胃郁热证患者小于1年、1-5年明显比超过5年的患者多; 中虚气逆证患者1-5年、大于5年明显比小于1年多; 痰瘀互结证患者病程大于5年明显比小于1年患者多, 差异均有统计学意义(P<0.05). 血浆脑肠肽水平与病程有关: 病程大于5年患者血浆促胃动素(motilin, MTL)水平显著低于病程小于1年患者, 差异有统计学意义(P<0.05), 3组间血浆MTL含量差异有统计学意义(P<0.05); 病程大于5年患者血浆5-羟色胺(5-hydroxytryptamine, 5-HT)、内皮素(endothelin, ET)高于病程1-5年及病程小于1年患者, 但无统计学意义.
结论: 不同中西医分型GERD患者病程并不相同, NERD患者比RE患者病程容易迁延, 病程长的GERD患者常表现为中虚气逆、痰瘀互结证, 血浆5-HT、ET、MTL可能和GERD患者病情的反复、迁延有关.
核心提示: 胃食管反流病(gastroesophageal reflux disease, GERD)是指胃、十二指肠内容物反流进入食管内, 引起各种反流症状和并发症的一种疾病. 本文重在探讨GERD患者中医证型、脑肠肽变化水平与病程之间的关系.
引文著录: 陈莉丽, 卜平, 方晓华. 脑肠肽、中医证型与胃食管反流病病程的相关性. 世界华人消化杂志 2016; 24(16): 2531-2536
Revised: April 27, 2016
Accepted: May 9, 2016
Published online: June 8, 2016
AIM: To investigate the relationship between plasma brain gut peptides, traditional Chinese medicine (TCM) syndrome and the course of gastroesophageal reflux disease (GERD).
METHODS: One hundred and sventy-eight GERD patients were included. They had five TCM syndromes: liver stomach heat, gas exchange resistance, phlegm stagnation and blood stasis, Qi deficiency, and Qi stagnation and blood stasis. Plasma levels of brain gut peptides including 5-hydroxytryptamine, somatostatin, vasoactive intestinal peptide, endothelin, and motilin were detected.
RESULTS: In the 178 patients with GERD, the proportion of patients with liver stomach heat syndrome was significantly higher in the reflux esophagitis (RE) group than in the non-erosive gastroesophageal reflux disease (NERD) group (P < 0.05), while the proportions of patients with phlegm stagnation and blood stasis syndrome and Qi deficiency syndrome were significantly higher in the NERD group than in the RE group (P < 0.05). Of the 178 GERD patients, 73 (41%) had a disease course < 1 year, 72 (40.5%) had a disease course between 1 and 5 years, and 33 (18.5%) had a course > 5 years. The proportion of patients with a course > 5 years was significantly higher in the NERD group than in the RE group (P < 0.05). The proportion of patients with a course < 1 year or between 1 and 5 years in patients with liver stomach heat syndrome was significantly higher that of patients with a course > 5 years (P < 0.05), the proportion of patients with a course between 1-5 years or > 5 years in patients with Qi deficiency syndrome was significantly higher than that of patients with a course < 1 year (P < 0.05), and the proportion of patients with a course > 5 years in patients with phlegm stagnation and blood stasis was significantly higher than that of patients with a course less than 1 year (P < 0.05). Motilin levels were significantly lower in patients with a course > 5 years than in patients with a course < 1 year (P < 0.05), and there was significant differences between the three groups (P < 0.05); 5-hydroxytryptamine and endothelin levels were higher in patients with a course > 5 years than in patients with a course between 1-5 years, but the difference was not significant.
CONCLUSION: The course of GERD patients with different TCM syndromes is different. The course of NERD patients is more likely to increase. GERD patients with a long course of disease often show Qi deficiency syndrome, liver stomach heat syndrome, and phlegm stagnation and blood stasis. Plasma 5-hydroxytryptamine, endothelin and motilin levels may be related to the prolongation of GERD.
- Citation: Chen LL, Bu P, Fang XH. Correlation between brain gut peptides, traditional Chinese medicine syndrome and course of gastroesophageal reflux disease. Shijie Huaren Xiaohua Zazhi 2016; 24(16): 2531-2536
- URL: https://www.wjgnet.com/1009-3079/full/v24/i16/2531.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v24.i16.2531
胃食管反流病(gastroesophageal reflux disease, GERD)是指胃、十二指肠内容物反流进入食管内, 引起各种反流症状和并发症的一种疾病. 其临床上表现为反酸、烧心、胸骨后灼痛、反食等典型症状, 也可同时合并有嗳气、恶心、咳嗽等非典型症状[1]. 随着生活水平、饮食结构等的变化, GERD的发病率逐年增加, 病程也容易反复、迁延, 严重影响人们的日常生活质量. 但导致GERD患者病情反复、迁延的原因并不明确, 也有研究[2-5]表明脑肠肽能够通过内分泌形式作用于胃肠道细胞的相应受体, 从而导致了GERD患者食管功能的改变及临床症状的产生. 但脑肠肽是否与病程迁延有关, 各种不同的中西医分型GERD患者病程有无区别, 目前未见相关报道.
选择2012-11/2014-01在苏北人民医院就诊的178例GERD患者为研究组, 采用GERD影响量表进行问诊采集病程, 并根据症状、舌象及脉象进行逐一辨证并予以中医分型. 本文研究参照国家技术监督局发布的《中药新药临床研究指导原则》有关证型的定义, 对病例进行逐一辨证分型, 分为5个证型: 肝胃郁热证、痰气交阻证、痰瘀互结证、中虚气逆证、气滞血瘀证. 入组的GERD患者皆行胃镜检查, 根据内镜下表现, 分为非糜烂性反流病(nonerosive reflux disease, NERD)组、反流性食管炎(reflux esophagitis, RE)组.
采用随机数字表法抽取接受问卷调查的GERD患者72例, 其中RE患者38例、NERD患者34例、健康体检者24例, 应用酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)进行血浆5-羟色胺(5-hydroxytryptamine, 5-HT)、胆囊收缩素、生长抑素(somatostatin, SS)、血管活性肠肽(vasoactive intestinal peptide, VIP)、促胃动素(motilin, MTL)、内皮素(endothelin, ET)检测. 外周血标本均经知情同意后取得.
统计学处理 使用SPSS19.0统计软件对资料进行统计分析, 以mean±SD表示, 计数资料则采用χ2检验, 计量资料之间的比较采用t检验, P<0.05表示差异有统计学意义.
178例GERD患者中, 肝胃郁热证87例, 占48.88%, 痰气交阻证45例, 占25.28%, 气滞血瘀证29例, 占16.29%, 中虚气逆证13例, 占7.30%, 痰瘀互结证4例, 占2.25%, RE及NERD组间比较, RE组肝胃郁热证较NERD明显升高, 差异有统计学意义(P<0.05), NERD组中虚气逆证、痰瘀互结证较RE组明显升高, 差异有统计学意义(P<0.05)(表1).
178例GERD患者中, 病程不足1年患者73例, 占41%. 病程1-5年患者72例, 占40.5%; 病程超过5年患者33例, 占18.5%; 其中NERD组病程超过5年的患者明显比RE组高, 差异有统计学意义(P<0.05), 而两组之间, 病程不足1年及病程1-5年的患者相比无明显统计学差异(P>0.05). 肝胃郁热证患者小于1年、1-5年明显比超过5年的患者多, 差异有统计学意义(P<0.05), 中虚气逆证患者1-5年、大于5年明显比小于1年多(P<0.05), 痰瘀互结证患者病程大于5年明显比小于1年患者多(P<0.05)(表2).
72例GERD患者中, 病程大于5年患者血浆MTL水平显著低于病程小于1年患者, 差异有统计学意义(P<0.05), 3组间血浆MTL含量差异有统计学意义(P<0.05); 病程大于5年患者血浆5-HT、ET高于病程1-5年及病程小于1年患者, 但无统计学意义(表3).
| 病程 | n | 5-HT(ng/mL) | CCK(ng/L) | SS(μg/L) | VIP(ng/L) | MTL(ng/L) | ET(ng/mL) |
| <1年 | 36 | 1394.80± 609.61 | 196.57±101.58 | 30.89±27.46 | 616.63±267.32 | 1314.40± 677.68 | 316.48±228.82 |
| 1-5年 | 22 | 1367.40± 949.18 | 281.31±188.41 | 28.65±24.13 | 679.73±198.26 | 889.12± 724.55 | 228.98±177.10 |
| >5年 | 14 | 1082.00± 547.98 | 165.99±135.49 | 30.70±22.98 | 627.12±253.16 | 292.49± 80.07a | 187.56±101.39 |
GERD是指胃、十二指肠内容物反流入食管引起胃灼热和反酸症状, 从而导致食管炎及咽喉、气道等食管以外的组织损害的疾病[6,7]. 发病原因主要为胃和食管交界处抗反流屏障异常、食管清除功能异常、胃内压力增高和排空功能障碍等[8]. GERD容易复发, 病程容易迁延, 患者需反复就诊, 不仅给患者带来躯体的痛苦, 而且也可造成巨大的精神压力以及经济负担.
GERD不同的中医证型在胃镜下表现不同, 病程也有其自身特征, 可用中医学的病因病机诠释. 在本文研究中, 肝胃郁热证87例, 占48.88%, 明显多于其他证型, 提示本证型与肝胃及火热之邪密切相关. 中医理论认为, 肝主疏泄, 肝气宜升, 喜条达, 恶抑郁; 胃受纳腐熟水谷, 主通降, 喜润恶燥. 若情志不遂, 肝失疏泄, 肝胃不和可致胆汁上逆, 胃灼热反酸; 肝气郁结, 气滞化火或郁久化热, 火热之邪为阳邪, 其性炎上, 易伤津耗气, 易生风动血, 易致疮疡. 故肝胃郁热证易致胆汁反流、食管黏膜充血灼伤, 甚则食管黏膜糜烂, 从而容易导致RE的发生. 本文研究亦证实RE组肝胃郁热证较NERD明显升高, 而NERD组中虚气逆证、痰瘀互结证较RE组明显升高. 其中NERD组病程超过5年的患者明显较RE组高, 说明NERD组患者病情迁延难愈. 究其原因, 与NERD组以中虚气逆证、痰瘀互结证这两个证型为主有关. 中虚气逆证中脾胃虚弱, 气虚不摄, 易致贲门松弛, 甚则形成裂孔疝, 病情危重, 恢复期长; 久病必虚, 气血化源不足或年高体衰, 精血亏损, 气阴渐伤, 阴损及阳, 中气衰败, 正气不支预后极差. 痰瘀互结证中痰瘀阻滞脉络, 一则加重脏腑气化之损害, 二则阻滞血液之循行, 导致气血循行不畅, 瘀血内停, 结而成块, 痰瘀互结易致食管黏膜受损难于修复, 充血、糜烂程度严重, 甚则形成溃疡[9,10], 病情较重, 迁延难愈. 这也证明了本文研究中中虚气逆、痰瘀互结这两个证型病程超过5年的患者明显较其他组多, 而肝胃郁热证病程小于1年的患者明显比超过5年的患者多. 对于病程迁延不愈的患者, 应该中西医结合, 注意中医辨证, 进行辨证施治, 可能对于促进患者的恢复, 缩短病程起到一定的作用.
胃肠道受中枢神经(central nervous system, CNS)、肠神经(enteric nervous system, ENS)、自主神经三层神经系统支配, 联系三层神经系统的神经内分泌网络被称为脑-肠轴[11-13], 机体通过脑肠轴能够进行胃肠功能的双向调节: 目前已发现20多种神经递质存在于CNS中, 而脑肠肽是其中最主要的神经递质[14,15]. 但脑肠肽是否和GERD患者病程有关并无相关报道, 在本文研究中, 5-HT、ET、MTL随着病程的延长而逐渐下降, 其中病程>5年患者血浆MTL水平显著低于病程<1年患者, 说明随着病程的延长, 部分收缩食管下段括约肌功能的脑肠肽水平下降, LESP压力会进一步下降, 容易导致反流症状的反复发作. 但5-HT、ET虽有下降, 无统计学意义, 尚需扩大样本量进一步研究. 不同中医证型的GERD患者病程不同, 可能和部分脑肠肽有一定的关系. 对于病程迁延不愈的患者, 及时进行脑肠肽的调整, 可能对于促进患者康复、缩短病程有一定的益处.
总之, 脑肠肽在GERD的发生、发展中起着重要的作用, 可能和GERD患者病情的反复、迁延有关. 不同中西医分型GERD患者病程并不相同, 临床治疗上应注意将西医辨病与中医辩证相结合, 注重区分中医证型, 对于病情迁延不愈的, 可以考虑针对中医辨证施治, 并对脑肠肽进行相应的调整, 从而对于缓解本病症状及预防复发取得更好的效果.
胃食管反流病(gastroesophageal reflux disease, GERD)发病的原因主要为胃和食管交界处抗反流屏障异常、食管清除功能异常、胃内压力增高和排空功能障碍等. 随着生活条件的改善、饮食结构等的改变, 患病率逐渐升高, 也容易迁延不愈.
禹正杨, 副教授, 南华大学附属第一医院
针对GERD流行病学调查的研究一直为热点之一, 但中医证型、脑肠肽与GERD之间关系未能深入研究.
有研究表明脑肠肽通过内分泌形式作用于胃肠道细胞的相应受体, 从而影响食管下段括约肌压力, 导致了GERD患者食管功能的改变及临床症状的产生.
本文通过对GERD患者进行中医证型分型, 并进行脑肠肽的测定, 探讨脑肠肽、中医证型与GERD患者病程的关系.
对于GERD病情迁延不愈的, 可以考虑针对中医辨证施治, 并对脑肠肽进行相应的调整, 从而对于缓解本病症状及预防复发取得更好的效果.
胃食管反流病(GERD): 是指胃内容物(包括十二指肠液)反流入食管产生症状或并发症. 典型症状有烧心、反酸、胸骨后疼痛, 其他还有恶心、嗳气、咽部不适、咳嗽、哮喘等.
本文有较好的学术价值, 值得进一步深入研究.
编辑:于明茜 电编:闫晋利
| 1. | Kase H, Hattori Y, Sato N, Banba N, Kasai K. Symptoms of gastroesophageal reflux in diabetes patients. Diabetes Res Clin Pract. 2008;79:e6-e7. [PubMed] [DOI] |
| 3. | Kim JH, Yamamoto T, Lee J, Yashiro T, Hamada T, Hayashi S, Kadowaki M. CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells. Biomed Res. 2014;35:285-293. [PubMed] [DOI] |
| 4. | Lim HC, Kim JH, Youn YH, Lee EH, Lee BK, Park H. Effects of the Addition of Mosapride to Gastroesophageal Reflux Disease Patients on Proton Pump Inhibitor: A Prospective Randomized, Double-blind Study. J Neurogastroenterol Motil. 2013;19:495-502. [PubMed] [DOI] |
| 5. | Zhao YH, Liu ZI, Li LH, Jiang SH, Shi CH. Systematic review of randomized controlled trials of traditional Chinese medicine treatment of non-acute bronchial asthma complicated by gastroesophageal reflux. J Tradit Chin Med. 2012;32:12-18. [PubMed] [DOI] |
| 6. | Altomare A, Guarino MP, Cocca S, Emerenziani S, Cicala M. Gastroesophageal reflux disease: Update on inflammation and symptom perception. World J Gastroenterol. 2013;19:6523-6528. [PubMed] [DOI] |
| 7. | Weijenborg PW, Smout AJ, Verseijden C, van Veen HA, Verheij J, de Jonge WJ, Bredenoord AJ. Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis. Am J Physiol Gastrointest Liver Physiol. 2014;307:G323-G329. [PubMed] [DOI] |
| 8. | Fallone CA, Barkun AN, Göttke MU, Best LM, Loo VG, Veldhuyzen van Zanten S, Nguyen T, Lowe A, Fainsilber T, Kouri K. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol. 2000;95:659-669. [PubMed] [DOI] |
| 11. | Brock C, Søfteland E, Gunterberg V, Frøkjær JB, Lelic D, Brock B, Dimcevski G, Gregersen H, Simrén M, Drewes AM. Diabetic autonomic neuropathy affects symptom generation and brain-gut axis. Diabetes Care. 2013;36:3698-3705. [PubMed] [DOI] |
| 12. | Okumura T. [Brain-gut interaction in the pathophysiology of IBS]. Nihon Shokakibyo Gakkai Zasshi. 2014;111:1334-1344. [PubMed] |
| 13. | Quigley EM. Bugs on the brain; brain in the gut--seeking explanations for common gastrointestinal symptoms. Ir J Med Sci. 2013;182:1-6. [PubMed] [DOI] |
| 14. | Rubenstein JH, Morgenstern H, McConell D, Scheiman JM, Schoenfeld P, Appelman H, McMahon LF, Kao JY, Metko V, Zhang M. Associations of diabetes mellitus, insulin, leptin, and ghrelin with gastroesophageal reflux and Barrett's esophagus. Gastroenterology. 2013;145:1237-1244.e1-e5. [PubMed] [DOI] |
| 15. | Talley NJ, Howell S, Poulton R. The irritable bowel syndrome and psychiatric disorders in the community: is there a link? Am J Gastroenterol. 2001;96:1072-1079. [PubMed] [DOI] |