Zhang M, Chen C Y, Hu Y, Lyu B
Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China (Zhang Meng is working on the Endoscopy Center of Wuhan City Jinyintan Hospital, Wuhan 430023, China).
Zhonghua Nei Ke Za Zhi. 2020 Jan 1;59(1):40-46. doi: 10.3760/cma.j.issn.0578-1426.2020.01.007.
To investigate the association between adherens junction proteins E-cadherin and β-catenin and tight junction protein claudin-2 and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome (IBS-D). Cecal biopsy tissues were collected from IBS-D patients (=26) according to Rome Ⅲ criterion and healthy controls (=26). The duration of symptoms, abdominal pain score and mean weekly bowel movements were recorded. Colorectal dilatation combined with restraint stress were applied to establish visceral hypersensitivity rat model. Abdominal contraction reflex (AWR) was applied to assess the visceral sensitivity in rats. The stool frequency within 1 hour was recorded after establishing the rat model. The expression of E-cadherin、β-catenin and claudin-2 were assessed by Western blot and immunofluorescence microscopy. Intercellular ultrastructure was observed by transmission electron microscopy. Compared with the healthy controls, the protein expression of E-cadherin and β-catenin in cecal epithelium in IBS-D patients were significantly lower (=0.015 and =0.005, respectively), while claudin-2 was significantly higher (=0.000). Reduced E-cadherin and β-catenin expression was associated high abdominal pain score (=-0.463, =0.017 and =-0.407, =0.039). The lower expression of β-catenin was associated with longer duration of symptoms (=-0.458, =0.019). The protein expression of E-cadherin and ß-catenin in the cecal epithelium of the visceral hypersensitivity rats were significantly lower (=0.004 and =0.003, respectively), while claudin-2 was significantly higher (=0.008). Reduced E-cadherin and ß-catenin expression was associated high visceral sensitivity in IBS-D rats (=-0.639, =0.047 and =-0.888, =0.001). Intercellular ultrastructure alterations well as cecal β-catenin and E-cadherin protein expression decrease and are associated with high abdominal pain score in IBS-D patients and hypersensitivity rats. β-catenin is further associated with prolonged duration of symptoms in IBS-D patients. The expression of E-cadherin and β-catenin may play a vital role in visceral sensitivity and intestinal barrier dysfunction in IBS-D.
探讨腹泻型肠易激综合征（IBS-D）患者中黏附连接蛋白E-钙黏蛋白和β-连环蛋白以及紧密连接蛋白claudin-2与临床症状之间的关联。根据罗马Ⅲ标准，从26例IBS-D患者和26例健康对照者中采集盲肠活检组织。记录症状持续时间、腹痛评分和平均每周排便次数。采用结直肠扩张联合束缚应激建立内脏高敏大鼠模型。应用腹部收缩反射（AWR）评估大鼠的内脏敏感性。建立大鼠模型后记录1小时内的粪便频率。通过蛋白质印迹法和免疫荧光显微镜评估E-钙黏蛋白、β-连环蛋白和claudin-2的表达。通过透射电子显微镜观察细胞间超微结构。与健康对照者相比，IBS-D患者盲肠上皮中E-钙黏蛋白和β-连环蛋白的蛋白表达显著降低（分别为P=0.015和P=0.005），而claudin-2显著升高（P=0.000）。E-钙黏蛋白和β-连环蛋白表达降低与高腹痛评分相关（r=-0.463，P=0.017和r=-0.407，P=0.039）。β-连环蛋白表达降低与症状持续时间延长相关（r=-0.458，P=0.019）。内脏高敏大鼠盲肠上皮中E-钙黏蛋白和β-连环蛋白的蛋白表达显著降低（分别为P=0.004和P=0.003），而claudin-2显著升高（P=0.008）。E-钙黏蛋白和β-连环蛋白表达降低与IBS-D大鼠的高内脏敏感性相关（r=-0.639，P=0.047和r=-0.888，P=0.001）。细胞间超微结构改变以及盲肠β-连环蛋白和E-钙黏蛋白蛋白表达降低与IBS-D患者和高敏大鼠的高腹痛评分相关。β-连环蛋白进一步与IBS-D患者症状持续时间延长相关。E-钙黏蛋白和β-连环蛋白的表达可能在IBS-D的内脏敏感性和肠道屏障功能障碍中起重要作用。
