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

Correlation of Anorectal Motility and Sensation with Peripheral Blood Mast Cell Tryptase in Diarrhea-predominant Irritable Bowel Syndrome Patients

背景腹泻型肠易激综合征(D-IBS)的病因由多因素参与,病理生理学机制复杂,至今尚未阐明。其中肛管直肠动力异常和内脏高敏感是参与的重要因素。高分辨率肛管直肠测压(HR-ARM)是一项对肛管直肠运动及感觉功能进行测定的新技术。肥大细胞类胰蛋白酶(MCT)是肥大细胞分泌的重要递质,其水平可作为肥大细胞活化程度的生物学标志。目的采用HR-ARM检测D-IBS患者是否具有肛管直肠动力及感觉功能异常,检测血MCT水平评估DdBS患者肥大细胞活化程度,验证血MCT水平与肛管直肠运动及感觉指标的相关性,探讨血MCT作为D-IBS生物学标志物的可能性。方法选取2014年8月—2016年11月于北京大学第一医院消化内科门诊就诊符合罗马Ⅲ标准的D-IBS患者21例为病例组,进行HR-ARM,检测肛管静息压、静息肛管最大收缩力、高压带长度,自主缩肛运动时肛门最大收缩压、持续挤压时间,模拟排便时肛门残余压、肛门松弛率、直肠压力及直肠肛管压力差,直肠肛门抑制反射(RAIR)、初始感觉阈值、初始排便冲动阈值,最大耐受容量等。同时纳入同时期进行HR-ARM、完成上述指标检测且评估无异常的非D-IBS患者24例为对照组。应用竞争性抑制酶联免疫吸附试验(EHSA)检测血MCT水平。结果对照组与病例组肛管静息压、静息肛管最大收缩力、自主缩肛运动时持续挤压时间、模拟排便时肛门松弛率、RAIR、最大耐受容量比较,差异均无统计学意义(P>0.05);病例组静息高压带长度、自主缩肛运动时肛门最大收缩压、模拟排便时肛门残余压、直肠压力、直肠肛管压力差较对照组升高,初始感觉阈值、初始排便冲动阈值较对照组降低(P<0.05)。对照组血MCT水平为(15.28±2.66)μg/L,低于病例组的(22.24±7.66)μg/L(Z=-3.628,P<0.01)。Spearman相关性分析显示,D-IBS患者血MCT水平与初始感觉阈值呈负相关(r_s=-0.524,P=0.015)。结论 HR-ARM可作为临床检测DdBS患者肛管直肠动力及感觉功能异常的有效手段;血MCT可作为D-IBS的有效生物标志物进一步探讨,并与肛管直肠初始感觉阈值相关。

Background The etiologies of diarrhea-predominant irritable bowel syndrome（D-IBS） are multifactorial,and the pathophysiological mechanisms remain incompletely understood due to their complicacy.Anorectal motility disorders and visceral hypersensitivity have been proved to be highly prevalent in D-IBS.To measure the anorectal motility and sensation,a new technique with high-resolution anorectal manometry（HR-ARM） is emerging in clinical practice.Mast cell tryptase（MCT） is an important mediator secreted by mast cell and its level has been suggested to be an excellent biomarker for mast cell activation.Objective The current study was to appraise the status of anorectal motility and sensation by HR-ARM,as well as the degree of mast cell activation in D-IBS patients by measured MCT levels.The relationship between plasma MCT levels and indicators of anorectal motility and sensation was further determined to establish the feasibility of serum MCT as a biomarker of D-IBS.Methods From the Gastroenterology Outpatient of Peking University First Hospital between August 2014 and November2016,we recruited 21 D-IBS patients with symptoms meeting the Rome-Ⅲ criteria（case group）,and 24 healthy controls with normal results of anorectal manometry（control group）.Both groups underwent HR-ARM for detecting the anal canal resting pressure,anal canal maximum squeeze pressure under quiescent conditions,high-pressure zone length（HPZL）,anal sphincter maximum squeeze pressure and anal sphincter squeeze duration during voluntary anal contraction,anal residual pressure,anal relaxation rate,rectal pressure and rectoanal gradient during simulated evacuation,rectoanal inhibitory reflex（RAIR）,first sensation threshold,first desire to defecate threshold,rectal maximum tolerable volume and so on.Plasma MCT titers were identified by competitive inhibition enzyme-linked immunosorbent assay（ELISA）.Results No significant differences were found between the two groups in terms of anal canal resting pressure,anal canal maximum squeeze pressure under quiescent conditions,anal sphincter squeeze duration during voluntary anal contraction,anal relaxation rate during simulated defecation,RAIR and rectal maximum tolerable volume（P〈0.05）.Compared to the control group,the values of HPZL,anal sphincter maximum squeeze pressure during voluntary anal contraction,anal residual pressure,rectal pressure,and rectoanal gradient during simulated evacuation were significantly higher in case group（P〈0.05）,while the values of first sensation threshold and first desire to defecate threshold were significantly lower in case group（P〈0.05）.Plasma MCT level was significantly higher in case group than in the control group[（22.24 ± 7.66） μg/L vs.（15.28 ± 2.66）μg/L,Z=-3.628,P〈0.01）.Spearman＇s rank correlation coefficient analysis found that,there was a negative correlation between the plasma MCT level and first sensation thresholds in D-IBS patients（rs =-0.524,P =0.015）.Conclusion HR-ARM can effectively detect the anorectal motility and sensation abnormalities in D-IBS patients.Being related to the first sensation threshold,plasma MCT levels are suggested as potential markers to establish the diagnosis of D-IBS.