Clinical Response and Changes in Intestinal Barrier Function，Inflammatory Markers and Neuropeptide Y among Diarrhea-predominant Irritable Bowel Syndrome with Liver-qi Stagnation and Spleen Deficiency Syndrome Patients Treated with Anchang Decoction

doi:10.12114/j.issn.1007-9572.2019.00.569

Abstract

Abstract: Background　Diarrhea-predominant irritable bowel syndrome（IBS-D） is a common disease and frequently-occurring disease of digestive system.Clinical responses to western medicine treatment scheme in IBS-D patients are not significant，especially the improvement of visceral sensitivity is unsatisfied.Furthermore，the patients are prone to recurrence after the treatment.So it is necessary to find a more effective treatment.Objective　To explore clinical responses and changes in intestinal barrier function，inflammatory markers and neuropeptide Y（NPY） among IBS-D with liver-qi stagnation and spleen deficiency syndrome patients treated with Anchang Decoction Methods　Sixty-four IBS-D gastroenterology outpatients and inpatients meeting the research criteria from Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine were enrolled from February to December 2018.By use of a random number table，they were evenly divided into the control group and observation group，treated with 8-week oral administration of Trimebutine Maleate Capsule，Trimebutine Maleate Capsule with Anchang Decoction，respectively.Clinical efficacy，and pre-and post-treatment Irritable Bowel Syndrome Quality of Life（IBS-QOL） score，Hamilton Anxiety Rating Scale（HAMA） score，Hamilton Depression Rating Scale（HAMD） score，serum levels of diamine oxidase（DAO），D-lactate，intestinal fatty-acid binding protein（I-FABP），interleukin-6（IL-6），interleukin-8（IL-8），tumor necrosis factor-alpha（TNF-α），and NPY were measured.Results　The overall clinical response of the observation group was better than that of the control group（Z=2.163，P<0.05）．After treatment，the observation group showed higher average IBS-QOL score and lower average HAMA and HAMD scores than the control group（P<0.05）．The average IBS-QOL score increased and average HAMA and HAMD scores decreased significantly in both groups after treatment（P<0.05）．The average post-treatment serum levels of DAO，D-lactate and IFABP of the observation group were significantly lower than those of the control group（P<0.05）．The average serum levels of DAO，D-lactate and IFABP decreased significantly in both groups after treatment compared with baseline（P<0.05）．After treatment，the observation group showed lower average serum levels of IL-6，IL-8 and TNF-α and higher average serum NPY than the control group（P<0.05）．The average serum levels of IL-6，IL-8 and TNF-α decreased and serum NPY increased significantly in both groups after treatment（P<0.05）．Conclusion　Anchang Decoction is effective in treating IBS-D with liver-qi stagnation and spleen deficiency.It can improve the overall quality of life，relieve anxiety and depression，improve intestinal barrier function，protect intestinal tissue，alleviate inflammation，regulate and control the secretion balance of brain-gut peptide in these patients.

Key words: Irritable bowel syndrome, Hepatic stagnation and splenic deficiency, Anchang decoction, Intestinal barrier function, Inflammatory factors, Neuropeptide Y level, Brain-gut peptide, Treatment outcome

摘要： 背景　腹泻型肠易激综合征（IBS-D）作为消化系统的常见病和多发病之一，目前单纯应用西医治疗方案对于IBS-D患者的诊疗特别是内脏敏感性的调节治疗效果不够显著，且容易复发。目的　探讨安肠汤治疗IBS-D肝郁脾虚证患者的临床疗效及其对肠屏障功能、炎性因子、神经肽Y（NPY）水平的影响。方法　选取2018年2—12月在广西中医药大学附属瑞康医院消化内科住院及门诊就诊的符合研究标准的IBS-D肝郁脾虚证患者64例，依据随机数字表法分为对照组和观察组，各32例。对照组给予口服匹维溴铵片治疗，观察组在对照组的基础上口服安肠汤治疗，两组患者治疗疗程均为8周。比较两组患者临床疗效及治疗前后肠易激综合征生活质量测试表（IBS-QOL）评分、汉密尔顿焦虑量表（HAMA）评分、汉密尔顿抑郁量表（HAMD）评分，血清二胺氧化酶（DAO）、D-乳酸、肠脂肪酸结合蛋白（IFABP）、白介素（IL）-6、IL-8、肿瘤坏死因子α（TNF-α）、NPY水平。结果　观察组患者临床疗效优于对照组（Z=2.163，P<0.05）。治疗后观察组IBS-QOL评分高于对照组，HAMA、HAMD评分低于对照组（P<0.05）。治疗后两组患者IBS-QOL评分高于同组治疗前，HAMA、HAMD评分低于同组治疗前（P<0.05）。治疗后观察组患者血清DAO、D-乳酸、IFABP水平低于对照组（P<0.05）。治疗后两组患者血清DAO、D-乳酸、IFABP水平均低于同组治疗前（P<0.05）。治疗后观察组患者血清IL-6、IL-8、TNF-α水平均低于对照组，血清NPY水平高于对照组（P<0.05）。治疗后两组患者血清IL-6、IL-8、TNF-α水平低于同组治疗前，血清NPY水平高于同组治疗前（P<0.05）。结论　安肠汤治疗IBS-D肝郁脾虚证患者的临床疗效显著，能够改善其整体生活质量和焦虑抑郁状态，改善肠屏障功能，保护肠组织，减轻炎性反应，调控脑肠肽分泌平衡。

关键词: 肠易激综合征, 肝郁脾虚证, 安肠汤, 肠屏障功能, 炎性因子, 神经肽Y水平, 脑肠肽, 治疗结果

CAI Linkun,HUANG Shi,PENG Zhuoyu, et al. Clinical Response and Changes in Intestinal Barrier Function，Inflammatory Markers and Neuropeptide Y among Diarrhea-predominant Irritable Bowel Syndrome with Liver-qi Stagnation and Spleen Deficiency Syndrome Patients Treated with Anchang Decoction　[J]. Chinese General Practice, 2020, 23(9): 1169-1174. DOI: 10.12114/j.issn.1007-9572.2019.00.569.
蔡林坤,黄适,彭卓嵛等. 安肠汤治疗腹泻型肠易激综合征肝郁脾虚证的临床疗效及其对肠屏障功能、炎性因子、神经肽Y水平的影响研究[J]. 中国全科医学, 2020, 23(9): 1169-1174. DOI: 10.12114/j.issn.1007-9572.2019.00.569.

References

［1］李超，迟雁，王化虹，等．腹泻型肠易激综合征患者肛管直肠动力及感觉功能与外周血肥大细胞类胰蛋白酶的相关性研究［J］．中国全科医学，2017，20（11）：1320-1325．DOI：10.3969/j.issn.1007-9572.2017.11.009.　
LI C，CHI Y，WANG H H，et al．Correlation of anorectal motility and sensation with peripheral blood mast cell tryptase in diarrhea-predominant irritable bowel syndrome patients［J］．Chinese General Practice，2017，20（11）：1320-1325．DOI：10.3969/j.issn.1007-9572.2017.11.009.
［2］彭卓嵛，蔡林坤，陶丽芬，等．资生颗粒联合生物反馈治疗腹泻型肠易激综合征临床研究［J］．亚太传统医药，2019，15（4）：126-128.　
PENG Z Y，CAI L K，TAO L F，et al．Clinical study on the effect of zisheng granule combined with biofeedback therapy in the treatment of diarrhea-predominant irritable bowel syndrome［J］．Asia-Pacific Traditional Medicine，2019，15（4）：126-128.
［3］POPA S L，LEUCUTA D C，DUMITRASCU D L.Pressure management as an occupational stress risk factor in irritable bowel syndrome：a cross-sectional study［J］．Medicine（Baltimore），2018，97（49）：e13562．DOI：10.1097/MD.0000000000013562.
［4］DROSSMAN D A.Functional gastrointestinal disorders：history，pathophysiology，clinical features and romeⅣ［J］．Gastroenterology，2016．DOI：10.1053/j.gastro.2016.02.032.
［5］LEE Y J，PARK K S.Irritable bowel syndrome：emerging paradigm in pathophysiology［J］．World J Gastroenterol，2014，20（10）：2456-2469．DOI：10.3748/wjg.v20.i10.2456.
［6］LOVELL R M，FORD A C.Global prevalence of and risk factors for irritable bowel syndrome：a meta-analysis［J］．Clin Gastroenterol Hepatol，2012，10（7）：712-721.e4．DOI：10.1016/j.cgh.2012.02.029.
［7］古巧燕，张军.肠易激综合征发病机制研究新进展［J］．胃肠病学和肝病学杂志，2017，26（12）：1420-1423．DOI：10.3969/j.issn.1006-5709.2017.12.024.　
GU Q Y，ZHANG J.The research advances in the pathogenesis of irritable bowel syndrome［J］．Chinese Journal of Gastroenterology and Hepatology，2017，26（12）：1420-1423．DOI：10.3969/j.issn.1006-5709.2017.12.024.
［8］陈军亮，樊志敏.肠屏障功能常用血清学检测现状及进展［J］．结直肠肛门外科，2009，15（3）：207-209．DOI：10.3969/j.issn.1674-0491.2009.03.034.　
［9］HYLAND N P，QUIGLEY E M，BRINT E.Microbiota-host interactions in irritable bowel syndrome：epithelial barrier，immune regulation and brain-gut interactions［J］．World J Gastroenterol，2014，20（27）：8859-8866．DOI：10.3748/wjg.v20.i27.8859.
［10］黄鹤飞，陈颖，朱晓新，等．中药干预肠易激综合征的脑肠肽调节研究进展［J］．中国实验方剂学杂志，2016，22（11）：208-217．DOI：10.13422/j.cnki.syfjx.2016110208.　HUANG H F，CHEN Y，ZHU X X，et al．Traditional Chinese medicine intervention regulates brain-gut peptides of irritable bowel syndrome［J］．Chinese Journal of Experimental Traditional Medical Formulae，2016，22（11）：208-217．DOI：10.13422/j.cnki.syfjx.2016110208.
［11］XU X J，LIU L，YAO S K.Nerve growth factor and diarrhea-predominant irritable bowel syndrome（IBS-D）：a potential therapeutic target?［J］．J Zhejiang Univ Sci B，2016，17（1）：1-9．DOI：10.1631/jzus.B1500181.
［12］张声生，魏玮，杨俭勤.肠易激综合征中医诊疗专家共识意见（2017）［J］．中医杂志，2017，58（18）：1614-1620．DOI：10.13288/j.11-2166/r.2017.18.024.
［13］蔡林坤，黄适，彭卓嵛，等.从内脏敏感性角度探讨安肠汤治疗腹泻型肠易激综合征的临床疗效及其对血清5-羟色胺水平的影响研究［J］．中国全科医学，2019，22（36）：4488-4492，4498．DOI：10.12114/j.issn.1007-9572.2019.00.533．
［14］郑筱萸.中药新药临床研究指导原则：试行［M］．北京：中国医药科技出版社，2002：54-58.
［15］HOU X H，CHEN S L，ZHANG Y L，et al．Quality of life in patients with Irritable Bowel Syndrome（IBS），assessed using the IBS-Quality of Life（IBS-QOL） measure after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide：results of an international prospective observational cohort study in Poland，Egypt，Mexico and China［J］．Clin Drug Investig，2014，34（11）：783-793．DOI：10.1007/s40261-014-0233-y.
［16］HAMILTON M.The assessment of anxiety states by rating［J］．Br J Med Psychol，1959，32（1）：50-55．DOI：10.1111/j.2044-8341.1959.tb00467.x.
［17］HAMILTON M.Development of a rating scale for primary depressive illness［J］．Br J Soc Clin Psychol，1967，6（4）：278-296.
［18］张声生，汪红兵，李振华，等．360例腹泻型肠易激综合征的聚类分析及证候特征研究［J］．中华中医药杂志，2010，25（8）：1183-1187.　
ZHANG S S，WANG H B，LI Z H，et al．Cluster analysis and characteristics of syndrome on IBS-D：a study of 360 cases［J］．China Journal of Traditional Chinese Medicine and Pharmacy，2010，25（8）：1183-1187.
［19］黄幼异，黄伟，孙蓉.柴胡皂苷对肝脏的药理毒理作用研究进展［J］．中国实验方剂学杂志，2011，17（17）：298-301．DOI：10.3969/j.issn.1005-9903.2011.17.088.　
［20］冯文林，伍海涛，罗超华.白芍总苷在消化系统疾病中的药理研究进展［J］．时珍国医国药，2012，23（7）：1778-1779．DOI：10.3969/j.issn.1008-0805.2012.07.087.　
［21］王晶，张世洋，盛永成，等．白术治疗胃肠道疾病药理作用研究进展［J］．中华中医药学刊，2018，36（12）：2854-2858．DOI：10.13193/j.issn.1673-7717.2018.12.008.　WANG J，ZHANG S Y，SHENG Y C，et al．Research progress on pharmacological actionof baizhu in treatment of gastrointestinal diseases［J］．Chinese Archives of Traditional Chinese Medicine，2018，36（12）：2854-2858．DOI：10.13193/j.issn.1673-7717.2018.12.008.
［22］刘双利，姜程曦，赵岩，等．防风化学成分及其药理作用研究进展［J］．中草药，2017，48（10）：2146-2152．DOI：10.7501/j.issn.0253-2670.2017.10.032.　
［23］俞静静，苏洁，吕圭源.陈皮抗心脑血管疾病相关药理研究进展［J］．中草药，2016，47（17）：3127-3132.
［24］章斌，金剑，金芝贵，等．枳壳的药理作用与临床应用进展［J］．医药导报，2013，32（11）：1462-1464.
［25］黄险峰，彭国平.香附的化学成分及药理研究进展［J］．中药材，2003，26（1）：65-68．DOI：10.3321/j.issn：1001-4454.2003.01.029.
［26］杜旌畅，谢晓芳，熊亮，等．川芎挥发油的化学成分与药理活性研究进展［J］．中国中药杂志，2016，41（23）：4328-4333.　
DU J C，XIE X F，XIONG L，et al．Research progress of chemical constituents and pharmacological activities of essential oil of Ligusticum chuanxiong［J］．China Journal of Chinese Materia Medica，2016，41（23）：4328-4333.
［27］高雪岩，王文全，魏胜利，等．甘草及其活性成分的药理活性研究进展［J］．中国中药杂志，2009，34（21）：2695-2700．DOI：10.3321/j.issn：1001-5302.2009.21.001.　
［28］KENNEDY P J，CRYAN J F，QUIGLEY E M，et al．A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome［J］．Psychol Med，2014，44（14）：3123-3134．DOI：10.1017/S003329171400052X.
［29］GOULET O，RUEMMELE F，LACAILLE F，et al．Irreversible intestinal failure［J］．J Pediatr Gastroenterol Nutr，2004，38（3）：250-269.
［30］K?NIG J，WELLS J，CANI P D，et al．Human intestinal barrier function in health and disease［J］．Clin Transl Gastroenterol，2016，7（10）：e196．DOI：10.1038/ctg.2016.54.
［31］程源.D-乳酸与I-FABP在肠屏障功能受损中作用的研究进展［J］．中国临床新医学，2018，11（9）：949-953．DOI：10.3969/j.issn.1674-3806.2018.09.31.　

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