功能性消化不良的中西醫(yī)研究進(jìn)展

【摘要】功能性消化不良(functional dyspepsia，F(xiàn)D)是臨床上最常見(jiàn)的一種功能性胃腸病，極大地影響了人們的生活質(zhì)量。FD的發(fā)病機(jī)制至今尚未完全闡明?？赡芘c胃腸運(yùn)動(dòng)功能障礙、內(nèi)臟高敏感性、基因易感性、腦腸軸功能失調(diào)、心理社會(huì)因素以及感染等有關(guān)。西醫(yī)采用促進(jìn)胃動(dòng)力、抑酸、根除幽門(mén)螺旋桿菌等治療，中醫(yī)藥從整體出發(fā)，多層次、多靶點(diǎn)、多途徑對(duì)胃腸運(yùn)動(dòng)、胃腸激素等進(jìn)行調(diào)節(jié)，近年來(lái)取得了一定進(jìn)展。

［doi: 10．3969/j．issn．1006-7795．2015．04．027］·轉(zhuǎn)化醫(yī)學(xué)研究·

基金項(xiàng)目:北京市醫(yī)院管理局臨床醫(yī)學(xué)發(fā)展專(zhuān)項(xiàng)經(jīng)費(fèi)資助(ZYLX201411)，北京市衛(wèi)生系統(tǒng)高層次衛(wèi)生技術(shù)人才培養(yǎng)計(jì)劃(2011-2-13)，北京市十病十藥-仁術(shù)健脾理氣顆粒臨床前研究(Z131100002513012)。This study was supported by Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201411)，Project of Health Technical Personnel of Beijing Health System(2011-2-13)，Beijing Ten Disease of Ten Drugs-Renzhu Jianpi Liqi Granules Pre Clinical Study(Z131100002513012)．* Corresponding author，E-mail: zhss2000@ 163．com

網(wǎng)絡(luò)出版時(shí)間: 2015－07－16 23∶15網(wǎng)絡(luò)出版地址: http:∥www．cnki．net/kcms/detail/11．3662．r．20150716．2315．031．html

Research progress of functional dyspepsia in Chinese medicine

Zhang Shengsheng *，Li Xiaoling

(Digestive Disease Center，Beijing Hospital of Traditional Chinese Medicine，Capital Medical University，Beijing 100010，China)

【Abstract】　Functional dyspepsia is a most common functional gastrointestinal disease affecting people＇s daily life．The etiology and pathogenesis of FD has not been fully elucidated．Western medicine diagnostic typing remains controversial while Chinese medicine treatment of FD shows great advantage．

【Key words】functional dyspepsia; etiology and pathogenesis; treatment

Functional dyspepsia(FD)is a group of persistent or recurrent digestive system symptoms which is currently no organic cause ［1］，including postprandial fullness discomfort，epigastric fullness，belching，abdominal pain，and anorexia．Epidemiological investigation shows that the incidence of FD in European and American population was 19%-41%，18%-45% in China ［2］．Study on the pathophysiological mechanism of FD and the effective treatment has been a hot spot in domestic and international field of gastroenterology．The following review focuses on the research progress of FD in the pathogenesis and diagnostic methods．

1　Pathogenesis

1．1 Western medicine pathogenesis

The etiology and pathogenesis of FD have not been fully elucidated，it is assumed that the possible pathophysiology associated with HP infection，gastrointestinal motility disorders，brain-gut visceral psychosocial factors，sensitivity，axis dysfunction and a genetic predisposition，focusing on gastrointestinal motility disorders and psychosocial factors．In recent years，with the understanding of FD，there is a shift from the single disease mode to biology and sociopsychologic mode which is based on the brain gut axis dysfunction．

Some researchers think that，helicobacter pylori(HP)infection may be involved in the pathogenesis of FD．Keohane et al． ［3］found that in the research on association between HP infection and the pathophysiology of FD，mast cells(MC)activation caused by HP infection may be involved in the pathophysiological process of FD．A randomized，double blind，control led clinical studywhich was performed on 158 cases of patients with FD showed that the eradication of HP infection can improve the symptoms of FD ［4］．Although many data showed that HP infection and FD are closely related，but epidemiological studies have failed to confirm a close correlation between HP infection and FD．Therefore，the relationship between HP infection and FD remains to be further studied．

Gastric motility disorder has been considered to be the principal pathophysiological basis of FD，most of the FD patients had gastric antrum，duodenum movement abnormality and gastric juice，gastric emptying disorder，but this theory can only explain part of the symptoms．Ke et al． ［5］found that there has been significant delay of gastric solid and liquid food emptying in patients with FD．The Kusanu et al． ［6］study found that not gastric emptying delayed，but gastric emptying accentuation is more likely to result in FD．If so，it may aggravate the symptoms in the process of taking prokinetic drugs．

The study found that the proportion of mentally abnormal patients with FD was significantly higher than that of healthy people．FD patients lack of personality characteristics．In the different study，we can see FD patients with various mental disorders such as anxiety，depression and interpersonal sensitivity ［7-11］．Animal studies found that acute mental stress easy to increase the body＇s sensitivity to visceral stimuli ［12］．Stress is likely to be through a central pathway to influence peripheral sensorimotor function．

FD patients are common with visceral sensitivity，increased sensitivity of stomach and duodenum to mechanical expansion，reduced the sensory thresholds and threshold capacity to acid．Talley et al． ［13］found that 40% of FD patients have impaired proximal gastric accommodation，making gastric mechanoreceptor activation induces early satiety．The specific mechanisms of visceral sensitivity reaction is not yet clear，presumably being relevant with the brain－gut axis regulation，gastric acid stimulation and gastrointestinal hormones．

Brain gut axis is a huge neuro-endocrine network which is composed of the body of the central nervous system，enteric nervous system and brain gut peptide．The enteric nervous system in the gastrointestinal tract is independent of the central nervous system，it can synthesize and release brain gut peptides．Brain gut peptides are also present in the central nervous system; they have the dual function of neurotransmitters and hormones，and are involved in the pathophysiology of FD．

Recent studies have found that G protein beta 3 subunit gene polymorphisms associated with digestive symptoms，but whether the genotype changes are associated with a particular pathophysiological mechanism，post infectious functional lesion or sociopsychological factors relevant to the gene change and genetic factors，need further study．

1．2 Pathogenesis of FD according to traditional Chinese medicine

The ancient discussions on the pathogenesis of FD can be seen in“Su Wen and Bi Lun”，e．g．，“Eating too much may hurt the stomach”;“Su Wen and Ju Tong Lun”states:“If the stomach was assaulted by cold qi，people will have stomach pain and vomiting”; Gao Li in the“Spleen and Stomach”mentions:“gas in the Yang，may cause disorder in the breast，even fully block”; Jing-yue Zhang put forward in“Jing Yue Quan Shu”states:“Anger burst injury，liver qi is not flat and the emergence of fullness”; Jin-ao Shen in the“Origin of rhino candle and miscellaneous diseases”said:“The fullness is due to spleen disease，the spleen deficiency and stagnation of qi can induce the epigastric problem”．Clearly，the ancient physicians believe that the etiology and pathogenesis of the disease are mainly related to improper diet，cold invasion，exterior evil invagination，emotional discord，weakness of the spleen and stomach．

In“Dyspepsia TCM Treatment Consensus” ［14］，which was promulgated in 2010，it was described that FD belongs to the following Chinese medicine category，such as“Fullness”，“Stomachache”，and“Stagnation”．The incidence of multiple symptoms might be caused by the weakness of the spleen and stomach，improper diet，emotionally not smooth，dampness and heat，deficiency of stomach yin．Diseased parts is in the stomach，might involve liver and spleen．The pathogenesis is deficiency in origin and excess in superficiality，deficiency beingmixed up with excess; the spleen deficiency is origin and the stagnation of qi，blood stasis，phlegm and dampness，dyspepsia becomes superficial．The syndrome of spleen deficiency and qi stagnation are the pathological link throughout the total progress of disease．

2　Diagnosis and syndrome differentiation

2．1 Diagnostic classification

According to Rome III standard of 2006，F(xiàn)D is divided into postprandial distress syndrome(PDS)，epigastric pain syndrome(EPS)and mixed type three subtypes，but this kind of classification method is still controversial．Song et al． ［15］found that there were no significant differences in gastric emptying，gastric myoelectric activity and autonomic nerve function，gastric liquid load test，gastric internal pressure test and the psychological assessment of FD three subtypes．It is suggested that the typing method is difficult to distinguish FD which has different pathophysiological mechanisms，we should look for more scientific typing method．

2．2 Syndrome differentiation

In“Dyspepsia TCM Treatment Consensus” ［14］of 2010，F(xiàn)D is divided into spleen deficiency and qi stagnation，liver stomach disharmony，dampness and heat in spleen and stomach，spleen deficiency and cold heat complex five type．In the study of 565 FD patients syndrome distribution characteristics，Zhang et al． ［16］found that FD syndrome including the spleen deficiency and qi stagnation syndrome，damp heat in spleen and stomach，weakness of the spleen and stomach(cold)syndrome，syndrome of intermingled heat and cold syndrome four card type，these four types cover 95．2% patients．The spleen deficiency and qi stagnation syndrome of spleen stomach damp heat syndrome accounted for 46．4%，accounted for 22．3%，the weakness of the spleen and stomach(cold)symptoms accounted for 17．2%，accounting for 9．4% of cold and heat syndrome．

3　Treatment

3．1 Treatment of Western medicine

1)General treatment: Guiding FD patients to develop good eating habits，not smoking，not drinking alcohol and eating spicy or irritating foods and avoiding abuse of non steroidal anti-inflammatory drugs are important．Eating limited amount of food and eating foods with low fat content are recommended．

2)Drug treatment: There is no effective drugs for the treatment of FD，symptomatic treatment is recommended．Commonly used drugs include gastrointestinal prokinetic agents，acid suppression drugs，drugs for eradication of HP infection，and antidepressants．Prokinetic agents are dopamine receptor antagonists such as domperidone and itopride，5-HT4 receptor agonists such as levosulpiride and mosapride．Acid suppressive drugs mainly include H2 receptor antagonists，and proton pump inhibitors．Antidepressants are doxepin and flunarizine etc．Reduce the visceral hypersensitivity with granisetron．

3．2 Traditional Chinese medicine treatment

1)Empirical prescription treatment: Zhang et al． ［17］study showed that using modified Liu Jun Zi decoction on FD of spleen-deficiency and qi-stagnation syndrome significantly improved symptom score and gastric barium emptying of FD patients．Zhao et al． ［18］showed that Modified Ban Xia Xie Xin decoction can significantly improve symptom score of FD patients．

2)Self made prescription treatment: Zhang et al． ［19］used gastrosis No．1 compound to treat FD of spleen and stomach deficiency-cold syndrome，results showed that Gastrosis No．1 compound significantly improved dyspeptic symptoms score in FD patients．Wei et al． ［20］found that in rat model of anxiety type FD established by the tail clamp stimulation method，protein glutathione S-transferase Pi2(GSTP2)，superoxide dismutase(SOD2 2)，voltage dependent anion channel 1(VDAC-1)and neuron specific enolase(enolase)protein expression decreased in the model group．FD is associated with these proteins，the traditional Chinese medicine“Wei Kangning”can significantly improve these protein expression in rats．

3．3 Acupuncture therapy

The effect of acupuncture in the treatment of FD patients with dyspeptic symptoms was significantly superior to that of prokinetic drugs such as cisapride，domperi-done，and the acupuncture treatment has fewer side effects ［21］．Ren et al． ［22］reported that acupuncture could significantly improve gastric emptying of FD patients，which may be related to changes in hormone levels，suggesting that the acupuncture can improve gastrointestinal motor function in patients with FD．

4　Summary

To sum up，although the pathogenesis and treatment of FD have been widely studied，the mechanisms of FD are not fully elucidated．The typing method is difficult to distinguish FD which has different pathophysiological mechanisms，we should look for more scientific typing method．At present there is no effective drugs for the treatment of FD，in addition to symptomatic treatment，the gastroenterologists should pay attention to the psychological problems of Chinese medicine treatment of FD，but too few prospective multicenter，randomized，double blind，controlled strictly designed studies have been conducted and there are few reports about recurrence and prognosis of long-term efficacy．At present there is no internationally accepted FD animal model，no many animal experimental studies on FD have been reported，and the reliability is not high．Therefore，in the future，we should formulate scientific diagnostic typing method，establish good animal model，perfect the study on etiology，pathology and mechanism，conduct clinical research in strict accordance with the principles of randomized controlled trials(RCT)，strengthen the research on the longterm efficacy and recurrence，and lays the foundation for the treatment of FD．

5 References

［1］　Tack J，Talley N J，Camilleri M，et al．Functional Gastroduodenal Disorders［M］．Mclean: Regnon Associates，2006: 419-486．

［2］陳灝珠，林果為，王吉耀，等．實(shí)用內(nèi)科學(xué)［M］．北京:人民出版社，2013: 1938．

［3］　Keohane J，Quigley E M．Functional dyspepsia: the role of visceral hypersensitivity in it＇s pathogenesis［J］．World J Gastroenterol，2006，12(17): 2672-2676．

［4］　Ruiz García A，Gordillo López F J，Hermosa Hernán J C，et al．Effect of the helicobacter pylorieradieation in patients with functional dyspepsia: randomised placebo-controlled trial［J］．Med Clin: Barc，2005，124(11): 401-405．

［5］柯美云，谷成明，姜玉新，等．消化不良患者的胃幽門(mén)十二指腸運(yùn)動(dòng)協(xié)調(diào)性研究［J］．中國(guó)醫(yī)學(xué)科學(xué)院學(xué)報(bào)，2000，22(3): 240-24．

［6］　Kusanu M，Zai H，Shimoyama Y，et al．Rapid gastric emptying，rather than delayed gastric emptying，might provoke functional dyspepsia［J］．J Gastroenterol Hepatol，2011，26(3): 75-78．

［7］　Bennett E J，Piesse C，Palmer K，et al．Functional gastrointestinal disorders: psychological，social，and somatic features［J］．Gut，1998，42(3): 414-420．

［8］　Drossman D A．Gastrointestinal illness and the biopsychosocial model［J］．J Clin Gastroenterol，1996，22(4): 252-254．

［9］　Li Y，Nie Y，Sha W，et al．The link between psychosocial factors and dyspepsia: a epidemiological study［J］．Chin Med: Engl，2002，115(7): 1082-1084．

［10］Locke G R，Weaver A L，Melton L J，et al．Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study［J］．Am J Gastroenterology，2004，99(2): 350-357．

［11］Lee K J，Cha D Y，Cheon S J，et al．Plasma ghrelin levels and their relationship with gastric emptying in patients with dysmotility-like functional dyspepsia［J］．Digestion，2009，80(1): 58-63．

［12］Gunter W D，Shepard J D，F(xiàn)oreman R D，et al．Evidence for visceral hypersensitivity in high-anxiety rats［J］．Physiol Behav，2000，69(3): 379-382．

［13］Talley N J，Verlinden M，Jones H．Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia?［J］．Am J Gastroenterology，2001，96(5): 1422-1428．

［14］中華中醫(yī)藥學(xué)會(huì)脾胃病分會(huì)．消化不良中醫(yī)診療共識(shí)意見(jiàn)［J］．中華中醫(yī)藥雜志，2010，25(5): 722-725．

［15］宋志強(qiáng)，柯美云，王智鳳，等．不同分型功能性消化不良患者病理生理機(jī)制的比較研究［J］．中華醫(yī)學(xué)雜志，2010，30(10): 729-732．

［16］張聲生，陳貞，許文君，等．基于“寒、熱、虛、實(shí)”二次辨證的565例功能性消化不良證候分布特點(diǎn)研究［J］．中華中醫(yī)藥雜志，2008，23(9): 833-835．

［17］Zhang S，Zhao L，Wang H，et al．Efficacy of Modified Liujunzi decoction on functional dyspepsia of spleen-deficiency and qi-stagnation syndrome A randomized controlled trial ［J］．BMC Complement Altern Med，2013，13: 54．

［18］Zhao L，Zhang S，Wang Z，et al．Efficacy of Modified Banxia xie xin decoction on functional dyspepsia of cold and heat in complexity syndrome: a randomized controlled trial ［J］．Evid Based Complement Alternat Med，2013，2013: 812143．

［19］Zhang S S，Zhao L Q，Wang H B，et al．Efficacy of Gastrosis No．1 compound on functional dyspepsia of spleen and stomach deficiency－cold syndrome: a multi-center，doubleblind，placebo-controlled clinical tria［J］．Chin J Integr Med，2013，19(7): 498-504．

［20］Wei W，Li X，Hao J，et al．Proteomic analysis of stress rats via tail damping treated with traditional Chinese medicine“WeiKang ning”［J］．J Gastroenterol Hepatol，2011，26(9): 1425-1433．

［21］徐房龍，熊侈，概凝，等．功能性消化不良所屬針灸病譜等級(jí)的分類(lèi)依據(jù)及其思路［J］．中國(guó)針灸，2011，31(2): 189-192．

［22］任秦有，張超，黃裕新．針刺功能性消化不良患者足三里穴對(duì)其胃排空及相關(guān)激素水平影響的臨床研究［J］．山西醫(yī)科大學(xué)學(xué)報(bào)，2010，41(9): 819-821．

(收稿日期: 2012-02-11)

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