Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing 100069, China.
Department of Bioinformatics, College of Bioengineering, Capital Medical University, Beijing 100069, China.
Biomed Pharmacother. 2021 Jun;138:111479. doi: 10.1016/j.biopha.2021.111479. Epub 2021 Mar 25.
Constipation, mainly characterized by the difficulty in defecation, is a clinical symptom caused by a variety of factors. It can be manifested as normal or slow colonic transport abnormalities, which can occur alone or concurrently with defecation disorders. As there is not uniform definition and assessment standard, no clear plan could be used for the treatment of constipation. Although rhubarb, a traditional Chinese medicine, plays a therapeutic role in diseases involving constipation symptoms, the detailed mechanism of it in treating constipation remains unclear.
A model of constipation-induced by diphenoxylate was prepared. Immunofluorescent staining was used to detect the expression of mucin 2 (MUC2), calnexin and chymase in colon. Western blotting was used to detect changes of tryptase and calnexin in the colon. And real-time polymerase chain reaction (PCR) was utilized to detect the changes of immunoglobulin-binding protein (Bip), X-box binding protein 1 (Xbp1) and C/EBP homologous protein (CHOP) of colonic goblet cells in mRNA levels. ELISA and biochemical kits were utilized to detect the changes of MUC2, Trefoil factor 3 (TFF3), acetylcholine, histamine and C-C motif chemokine ligand 5 (CCL5) in the colon. And the changes of colonic mucosa and intestinal flora of constipation model mice caused by rhubarb extract (RE) were analyzed to identify the mechanism of RE on the treatment of constipation.
RE promotes the secretion of colonic mucus by recruiting mast cells and enhancing the content of histamine and Ach in the mice colon. In the process, RE causes up-regulation of Bip and CHOP mRNA expression and down-regulation of Xbp1 and Xbp1s mRNA expression that induces ER stress of colonic epithelium associated with changes in the intestinal flora diversity and short-chain fatty acids content.
RE could relieve constipation by promoting the secretion of colonic mucus via mast cells activation and improving the intestinal microenvironment.
便秘主要表现为排便困难，是由多种因素引起的临床症状。它可以表现为正常或缓慢的结肠转运异常，既可以单独发生，也可以与排便障碍同时发生。由于没有统一的定义和评估标准，因此无法针对便秘进行明确的治疗方案。虽然大黄作为一种中药，在涉及便秘症状的疾病中具有治疗作用，但它治疗便秘的详细机制尚不清楚。
制备地芬诺酯诱导的便秘模型。免疫荧光染色检测结肠中黏蛋白 2（MUC2）、钙连蛋白和糜酶的表达。Western blot 检测结肠中胰蛋白酶和钙连蛋白的变化。实时聚合酶链反应（PCR）检测结肠杯状细胞免疫球蛋白结合蛋白（Bip）、X 盒结合蛋白 1（Xbp1）和 C/EBP 同源蛋白（CHOP）mRNA 水平的变化。ELISA 和生化试剂盒检测结肠中 MUC2、三叶因子 3（TFF3）、乙酰胆碱、组胺和 C-C 基序趋化因子配体 5（CCL5）的变化。分析大黄提取物（RE）对便秘模型小鼠结肠黏膜和肠道菌群的影响，以确定 RE 治疗便秘的作用机制。
RE 通过招募肥大细胞和增强小鼠结肠中组胺和 Ach 的含量来促进结肠黏液的分泌。在此过程中，RE 导致 Bip 和 CHOP mRNA 表达上调，Xbp1 和 Xbp1s mRNA 表达下调，引起与肠道菌群多样性和短链脂肪酸含量变化相关的结肠上皮内质网应激。
RE 通过激活肥大细胞促进结肠黏液分泌，并改善肠道微环境来缓解便秘。
