特发性肛门瘙痒症患者直肠黏膜感觉受体表达情况研究

doi:10.12114/j.issn.1007-9572.2021.00.471

摘要/Abstract

摘要： 背景　对于特发性肛门瘙痒症，何种原因导致肛门潮湿、渗漏并刺激肛周皮肤感觉神经末梢而形成瘙痒-搔抓的恶性循环，目前仍不清楚。有研究表明，肛周皮肤潮湿、渗漏除受肛周菌群影响外，还可能与直肠感觉受体异常相关。目的　分析特发性肛门瘙痒症患者直肠黏膜感觉受体瞬时感受器电位香草酸受体1（TRPV1）、5-羟色胺（5-HT）、三磷酸腺苷受体受体P2X2抗体表达情况。方法　选取2017年1月—2019年6月浙江中医药大学附属第一医院肛肠外科与消化内科收治的门诊及住院特发性肛门瘙痒症患者30例作为瘙痒组，同期在浙江中医药大学附属第一医院体检健康者29例作为健康组。采用免疫组化、实时荧光定量聚合酶链式反应（PCR）检测两组受试者直肠黏膜组织TRPV1、5-HT、三磷酸腺苷受体受体P2X2抗体表达情况。结果　免疫组化结果显示，瘙痒组患者直肠黏膜组织TRPV1、5-HT呈阳性表达，三磷酸腺苷受体受体P2X2抗体呈阴性表达，且瘙痒组患者TRPV1平均光密度（MOD）值及HIS评分、5-HT MOD值及HIS评分高于健康组（P<0.01），而两组受试者直肠黏膜组织三磷酸腺苷受体受体P2X2抗体MOD值及HIS评分比较，差异无统计学意义（P>0.05）。实时荧光定量PCR结果显示，瘙痒组患者直肠黏膜组织TRPV1、5-HT mRNA相对表达量高于健康组（P<0.01），而两组受试者直肠黏膜组织三磷酸腺苷受体受体P2X2抗体mRNA相对表达量比较，差异无统计学意义（P>0.05）。结论　特发性肛门瘙痒症患者直肠黏膜感觉受体TRPV1、5-HT的表达明显升高，其直肠顺应性降低、感觉阈值升高可能与TRPV1、5-HT的过表达有关，并可能是由于直肠黏膜感觉传递中递质敏化或表型改变所致。

关键词: 肛门瘙痒症, 直肠, 肠黏膜, 感觉, TRPV阳离子通道, 5-羟色胺受体, 三磷酸腺苷受体受体P2X2抗体

Abstract: Background　It is not clear for what reason causes anal moisture and leakage to stimulate the sensory nerve endings of perianal skin and form a vicious circle of pruritus and scratching so far，but research has shown that perianal moisture and leakage may be related to the abnormity of rectal sensory receptors besides perianal flora.Objective　To analyze the expression of rectal mucosal sensory receptors in patients with idiopathic pruritus ani，including transient receptor potential vanilloid type 1（TRPV1），5-HT and P2RX2 polyclonal antibody.Methods　Participants were recruited from the First Affiliated Hospital of Zhejiang Chinese Medical University during January 2017 to June 2019，including 30 outpatients and inpatients with idiopathic pruritus ani（pruritus group）from Departments of Anorectal Surgery and Gastroenterology，and 29 physical examinees（healthy group）.Immunohistochemical method and real-time fluorescence quantitative polymerase chain reaction（PCR）were used to detect the expression of TRPV1，5-HT and P2RX2 polyclonal antibody in rectal mucosal tissue.Results　Immunohistochemical results showed that，TRPV1 and 5-HT were positively expressed but P2RX2 polyclonal antibody was negatively expressed in rectal mucosal tissue of pruritus group.MOD value and HIS score of TRPV1 and 5-HT in pruritus group were significantly higher than those in healthy group（P<0.01）.But there was no significant difference of MOD value or HIS score of P2RX2 polyclonal antibody between the two groups（P>0.05）.Real-time fluorescence quantitative PCR results showed that，the pruritus group had significantly higher relative expression quantity of mRNA of TRPV1 and 5-HT than healthy group（P<0.01），but there was no significant intergroup difference of relative expression quantity of mRNA of P2RX2 polyclonal antibody between the two groups（P>0.05）.Conclusion　The expression of rectal mucosal sensory receptors including TRPV1 and 5-HT significantly increase in patients with idiopathic pruritus ani，and the over-expression of TRPV1 and 5-HT may be related to reduced rectal compliance and increased rectal sensory threshold，which may be due to sensitization or phenotypic alteration of transmitters in rectal mucosal sensory transmission.

Key words: Pruritus ani, Rectum, Intestinal mucosa, Sensation, TRPV cation channels, 5- hydroxytryptamine receptors, P2RX2 polyclonal antibody

徐利,代群,何孝康,等. 特发性肛门瘙痒症患者直肠黏膜感觉受体表达情况研究[J]. 中国全科医学, 2021, 24(18): 2303-2308. DOI: 10.12114/j.issn.1007-9572.2021.00.471.
XU Li,DAI Qun,HE Xiaokang, et al. Expression of Rectal Mucosal Sensory Receptors in Patients with Idiopathic Pruritus Ani　[J]. Chinese General Practice, 2021, 24(18): 2303-2308. DOI: 10.12114/j.issn.1007-9572.2021.00.471.

参考文献

［1］中华中医药学会.中医肛肠科常见病诊疗指南［M］．北京：中国中医药出版社，2012：14.
［2］EYERS A A，THOMSON J P.Pruritus ani：is anal sphincter dysfunction important in aetiology？［J］．Br Med J，1979，2（6204）：1549-1551．DOI：https://doi.org/10.1136/bmj.2.6204.1549.
［3］GEPPETTI P，TREVISANI M.Activation and sensitisation of the vanilloid receptor：role in gastrointestinal inflammation and function［J］．Br J Pharmacol，2004，141（8）：1313-1320．DOI：10.1038/sj.bjp.0705768.
［4］BALEMANS D，BOECKXSTAENS G E，TALAVERA K，et al．
Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity［J］．Am J Physiol Gastrointest Liver Physiol，2017，312（6）：G635-648．DOI：10.1152/ajpgi.00401.2016.
［5］张勃然.辣椒素受体（TRPV1）在肠易激综合征患者结肠粘膜的表达研究［D］．苏州：苏州大学，2018.
［6］BRIERLEY S M，CARTER R，JONES W 3rd，et al．Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice［J］．J Physiol，2005，567（Pt 1）：267-281．DOI：10.1113/jphysiol.2005.089714.
［7］CHAN C L H，FACER P，DAVIS J B，et al．Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency［J］．Lancet，2003，361（9355）：385-391．DOI：10.1016/s0140-6736（03）12392-6.
［8］YAN C，LIU X G，WANG H H，et al．Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats［J］．Braz J Med Biol Res，2012，45（10）：948-954．DOI：10.1590/s0100-879x2012007500122.
［9］GERSHON M D.Nerves，reflexes，and the enteric nervous system：pathogenesis of the irritable bowel syndrome［J］．J Clin Gastroenterol，2005，39（5 Suppl 3）：S184-193.
［10］MATSUMOTO K，LO M W，HOSOYA T，et al．Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice［J］．Lab Invest，2012，92（5）：769-782．DOI：10.1038/labinvest.2012.14.
［11］吴璐一，翁志军，窦传字，等．针灸对IBS内脏痛大鼠结肠肌间神经丛神经元P2X2受体表达的调节［J］．世界中西医结合杂志，2014，9（6）：601-604．DOI：10.3969/j.issn.1673-6613.2014.06.014.
WU L Y，WENG Z J，DOU C Z，et al．Expression of P2X2 receptors in myenteric plexus neurons regulated with acupuncture in the rats with IBS visceral pain［J］．World Journal of Integrated Traditional and Western Medicine，2014，9（6）：601-604.
［12］DEVRIES M P，VESSALO M，GALLIGAN J J.Deletion of P2X2 and P2X3 receptor subunits does not alter motility of the mouse colon［J］．Front Neurosci，2010，4：22．DOI：10.3389/fnent.2010.00001.
［13］OHMAN L，SIMRéN M.New insights into the pathogenesis and pathophysiology of irritable bowel syndrome［J］．Dig Liver Dis，2007，39（3）：201-215．DOI：10.1016/j.dld.2006.10.014.
［14］WYNN G，RONG W，XIANG Z，et al．Purinergic mechanisms contribute to mechanosensory transduction in the rat colorectum［J］．Gastroenterology，2003，125（5）：1398-1409．DOI：10.1016/j.gastro.2003.07.008.
［15］徐利，葛琼翔，林国强.温和灸对肛门瘙痒模型小鼠背根节TRPV1表达的影响［J］．中国全科医学，2018，21（30）：3749-3752．DOI：10.12114/j.issn.1007-9572.2018.00.241.
XU L，GE Q X，LIN G Q.Effect of mild moxibustion on TRPV1 expression in the dorsal root ganglion in a mouse model of pruritus ani［J］．Chinese General Practice，2018，21（30）：3749-3752．DOI：10.12114/j.issn.1007-9572.2018.00.241.
［16］徐利.肛门瘙痒症患者肛管直肠动力学、肠黏膜感觉受体表达及艾灸干预的研究［D］．南京：南京中医药大学，2020．DOI：10.27253/d.cnki.gnjzu.2020.000227.
XU L.Reserch on anorectal dynamics and intestinal mucosal receptor expression in patients with pruritus ani and clinical study on moxibustion intervention［D］．Nanjing：Nanjing University of Chinese Medicine，2020．DOI：10.27253/d.cnki.gnjzu.2020.000227.

[1]	段玉霞, 李珍, 张斯齐, 房志学, 秦月兰. 结直肠癌诊疗中患者决策辅助工具应用效果的系统评价[J]. 中国全科医学, 2023, 26(25): 3194-3201.
[2]	张允旭, 王婷婷, 魏俊伶, 邢燕云, 苏莉. 影响女性身心健康的新病症：持续性生殖器官兴奋紊乱/生殖器官-骨盆感觉障碍综合征的研究现状及专家共识解读[J]. 中国全科医学, 2023, 26(23): 2830-2835.
[3]	苏海霞, 付兆媛, 高永泽, 尉戎戎, 钟建春. 5-羟色胺与腹泻型肠易激综合征相关性及中医药调控研究进展[J]. 中国全科医学, 2023, 26(21): 2678-2685.
[4]	胡佳艳, 吕咪, 王凤云. 抗生素对肠易激综合征的影响及机制探讨[J]. 中国全科医学, 2023, 26(21): 2666-2672.
[5]	陈璐璐, 张利苹, 李静文, 董文杰, 吴欣爱. 程序性死亡受体1抑制剂联合呋喹替尼后线治疗转移性结直肠癌的临床疗效和安全性研究[J]. 中国全科医学, 2023, 26(18): 2262-2267.
[6]	禹蓉, 董卫国, 田山, 王婷. 不同病理类型结直肠息肉癌变的临床研究进展[J]. 中国全科医学, 2023, 26(14): 1790-1794.
[7]	秦肖含, 张佩彦, 王玉珍. 功能性便秘患者临床症状和结直肠肛门功能检查分型的一致性研究[J]. 中国全科医学, 2023, 26(12): 1491-1495.
[8]	张芳芳, 胡雅静, 黄华勇, 倪锦晖, 尤泽, 常巧玲, 廖力. 基于CT诊断的肌少症对结直肠癌患者发生手术部位感染的影响因素分析[J]. 中国全科医学, 2022, 25(29): 3658-3663.
[9]	杜凯微, 姜霞, 王园园, 耿燕杰, 高天, 兰天昊, 王桂琦. 基于两种评分系统对结直肠癌根治术后并发症预测价值的研究[J]. 中国全科医学, 2022, 25(27): 3390-3394.
[10]	刘宇春, 阴丽霞, 高丽平, 丁兰, 丁静, 杜雪平, 于爽. 基层医生的儿童功能性便秘诊疗能力研究[J]. 中国全科医学, 2022, 25(25): 3150-3156.
[11]	张允旭, 苏莉, 邢燕云, 刘晓林, 王强. 姿势解密技术治疗持续性生殖器官兴奋紊乱/生殖器官-骨盆感觉障碍综合征一例并文献复习[J]. 中国全科医学, 2022, 25(17): 2169-2172.
[12]	冷欣颖, 邹华春, 付雷雯, 柯吴坚. 性传播感染导致的直肠炎、直肠结肠炎和肠炎的诊治要点——2021年美国CDC《性传播感染诊疗指南》分析[J]. 中国全科医学, 2022, 25(06): 651-655.
[13]	徐利，陈春花，何孝康，李敏. 有烟艾灸与无烟艾灸治疗肛门瘙痒症的临床效果对比及艾烟生成物的止痒效应研究[J]. 中国全科医学, 2021, 24(9): 1120-1124.
[14]	胡茜玥，刘正，王锡山. 结直肠癌筛查策略的研究现状与思考[J]. 中国全科医学, 2021, 24(33): 4165-4171.
[15]	韩西，刘君，马麒，呼圣娟. 我国结直肠癌筛查方案的研究进展及筛查困境分析[J]. 中国全科医学, 2021, 24(33): 4172-4176.