Katsumata Ryo, Shiotani Akiko, Murao Takahisa, Ishii Manabu, Fujita Minoru, Matsumoto Hiroshi, Haruma Ken
Division of Gastroenterology, Department of Internal medicine, Kawasaki Medical School, Japan.
Department of General Internal medicine 2, Kawasaki Medical School, Japan.
Intern Med. 2017;56(9):993-999. doi: 10.2169/internalmedicine.56.7674. Epub 2017 May 1.
Objective Gender differences, including differences in the prevalence, subtypes and the effectiveness of treatment, are generally recognized in irritable bowel syndrome (IBS). Although serotonin type 3 receptor (5-HT3R) antagonists appear to be more effective in women with diarrhea predominant IBS (IBS-D) than they are in men, the mechanisms underlying these effects remain unclear. The aim of the present was to investigate the gender differences in 5-HT signaling. Methods The subjects were selected from outpatients with IBS-D and healthy controls. Their rectal mucosal S100A, tryptophan hydroxylase (TPH) and 5-HT transporter (5-HTT, SERT, SLC6A4) mRNA expression levels were measured. Clinical symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS) and the self-rating depression scale (SDS). Results The study population of 100 subjects included 47 IBS-D patients and 53 age- and gender-matched healthy controls. The S100A9 (5.20 vs. 1.90, p=0.001) and SLC6A4 (2.00 vs. 1.00, p=0.019) mRNA levels in the rectal mucosa of women with IBS-D were significantly higher than those in men. Among the healthy controls, the S100A10 expression levels in men were higher than those in women (1.33 vs. 0.82, p=0.005). The S100A8 and S100A10 expression levels in women with IBS-D were positively correlated with their diarrhea scores (r=0.55 and 0.58, p<0.05). Conclusion 5-HT signaling might be a major contributor to the symptoms of IBS in men, and the differences may be associated with the effectiveness of 5-HT3R antagonists.
目的 肠易激综合征（IBS）中普遍存在性别差异，包括患病率、亚型及治疗效果的差异。虽然5-羟色胺3型受体（5-HT3R）拮抗剂对腹泻型IBS（IBS-D）女性患者似乎比对男性患者更有效，但其作用机制仍不清楚。本研究旨在探讨5-羟色胺（5-HT）信号通路中的性别差异。方法 研究对象选自IBS-D门诊患者及健康对照者。检测其直肠黏膜S100A、色氨酸羟化酶（TPH）及5-羟色胺转运体（5-HTT，SERT，SLC6A4）的mRNA表达水平。采用胃肠道症状评定量表（GSRS）和自评抑郁量表（SDS）评估临床症状。结果 100名研究对象中，包括47例IBS-D患者和53例年龄及性别匹配的健康对照者。IBS-D女性患者直肠黏膜中S100A9（5.20对1.90，p=0.001）和SLC6A4（2.00对1.00，p=0.019）的mRNA水平显著高于男性。在健康对照者中，男性的S100A10表达水平高于女性（1.33对0.82，p=0.005）。IBS-D女性患者的S100A8和S100A10表达水平与腹泻评分呈正相关（r=0.55和0.58，p<0.05）。结论 5-HT信号通路可能是男性IBS症状的主要影响因素，且这些差异可能与5-HT3R拮抗剂的疗效有关。
