Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.
Division of Gastroenterology & Hepatology, Loma Linda University Health, Loma Linda, CA, 92354, USA.
Dig Dis Sci. 2019 Mar;64(3):729-739. doi: 10.1007/s10620-018-5367-y. Epub 2018 Nov 16.
The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined.
To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model.
T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention.
Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice.
PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.
蛋白酶激活受体 2（PAR-2）在肠易激综合征（IBS）腹痛发病机制中的作用尚不清楚。
研究 PAR-2 介导的内脏敏感性在感染后肠易激综合征（PI-IBS）小鼠模型中的作用。
使用旋毛虫感染的 PI-IBS 小鼠模型。评估粪便丝氨酸蛋白酶活性和肠道肥大细胞。通过尿乳果糖/甘露醇比评估肠通透性，并通过 Western blot 检测结肠 PAR-2 和紧密连接（TJ）蛋白的表达。通过测量 Th（辅助性 T 细胞）1/Th2 细胞因子表达评估肠道免疫谱。通过测量对结肠扩张的腹壁退缩反射评估内脏敏感性。
与对照组相比，PI-IBS 小鼠结肠 PAR-2 表达、粪便丝氨酸蛋白酶活性和肠道肥大细胞计数均升高。与对照组相比，PI-IBS 小鼠结肠 TJ 蛋白表达降低，乳果糖/甘露醇比值升高，结肠 Th1/Th2 细胞因子比值升高，内脏敏感性增强。在对照组小鼠中给予 PAR-2 激动剂可观察到与 PI-IBS 小鼠相似的变化，而 PAR-2 拮抗剂可使 PI-IBS 小鼠中观察到的增加的肠道通透性和降低的内脏敏感性正常化。
PAR-2 激活增加肠道通透性，导致 PI-IBS 小鼠模型中的免疫激活和内脏敏感性增强。
