OBJECTIVE: To explore the therapeutic effect of BBP on ulcerative colitis and its potential mechanism by combining acute ulcerative colitis mouse models and comprehensively observing various physiological and biochemical indexes of mice.
METHODS: The acute ulcerative colitis model was induced by drinking water containing dextran sulfate sodium salt (DSS) for 7 days. Studies were divided into Control, DSS, DSS+ Sulfasalazine (SASP, 450 mg/kg), and DSS + bear bile powder group (BBP, 320 mg/kg). The Disease Activity Index (DAI) and colonic tissue damage of mice were evaluated. Tissue immunofluorescence and western blot were used to determine related tight Junction Proteins (TJs), and 16S V34 amplicon was used to analyze intestinal microorganisms. The therapeutic effect of BBP on ulcerative colitis model mice was studied comprehensively.
RESULTS: After treatment, BBP can significantly improve the physiological condition of acute UC mice and reduce DAI fraction. Compared with the DSS group, the BBP group significantly increased the colon length and significantly decreased the injury fraction of acute UC mice. Regarding the intestinal mechanical barrier, BBP significantly increased the expression of ZO-1, Occludin, and Claudin 1 protein in colon tissue. In terms of microbial community, the intestinal microbial diversity of mice decreased after the administration of BBP, but there was no significant difference in structural composition between the BBP group and the Control group. By comparing the four groups of species with significant differences, it was found that the BBP group significantly reduced the abundance of specific harmful microorganisms at the order, family, genus, and species levels.
CONCLUSIONS: Oral administration of a certain dose of BBP can significantly improve the symptoms of ulcerative colitis in mice. Part of the reason may be that it increases the expression of tight junction proteins, regulates specific flora in the intestine of mice, and maintains intestinal barrier homeostasis. In the future, the clinical application value of BBP will be explored, and BBP will be developed as a drug with the potential to treat UC and alleviate the pain of UC patients.
目的:结合急性溃疡性结肠炎小鼠模型,综合观察小鼠各项生理生化指标,探讨BBP对溃疡性结肠炎的治疗作用及其可能机制。
方法:用含葡聚糖硫酸钠(DSS)的水连续7天建立急性溃疡性结肠炎模型。研究分为对照,DSS,DSS+柳氮磺吡啶(SASP,450mg/kg),和DSS+熊胆粉组(BBP,320mg/kg)。评估小鼠的疾病活动指数(DAI)和结肠组织损伤。组织免疫荧光和蛋白质印迹用于确定相关的紧密连接蛋白(TJs),和16SV34扩增子用于分析肠道微生物。综合研究BBP对溃疡性结肠炎模型小鼠的治疗作用。
结果:治疗后,BBP能显著改善急性UC小鼠的生理状况,降低DAI分数。与DSS组相比,BBP组显著增加急性UC小鼠的结肠长度,显著降低损伤分数。关于肠道机械屏障,BBP显著增加ZO-1、Occludin、和结肠组织中的Claudin1蛋白。就微生物群落而言,小鼠肠道微生物多样性在服用BBP后降低,但BBP组与对照组在结构组成上无显著差异。通过比较四组具有显著差异的物种,发现BBP组显着降低了特定有害微生物的丰度,家庭,属,和物种水平。
结论:口服一定剂量的BBP可明显改善小鼠溃疡性结肠炎的症状。部分原因可能是它增加了紧密连接蛋白的表达,调节小鼠肠道中的特定菌群,并维持肠屏障稳态。在未来,探讨BBP的临床应用价值,BBP将被开发为具有治疗UC和缓解UC患者疼痛潜力的药物。