AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate th...AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.展开更多
目的本文通过探究葛根芩连汤“一方治三病”的作用机制,“三病”即溃疡性结肠炎、肠易激综合征和2型糖尿病,从实际范例中寻找中医药异病同治理论的应用证据。方法采用网络药理学方法,通过中药系统药理学数据库(Traditional Chinese medi...目的本文通过探究葛根芩连汤“一方治三病”的作用机制,“三病”即溃疡性结肠炎、肠易激综合征和2型糖尿病,从实际范例中寻找中医药异病同治理论的应用证据。方法采用网络药理学方法,通过中药系统药理学数据库(Traditional Chinese medicine systems pharmacology database,TCMSP)获取葛根芩连汤的主要活性成分及作用靶点,利用Gene cards、TTD、OMIM数据库获取溃疡性结肠炎、肠易激综合征和2型糖尿病3种疾病的相关靶点。将以上获得的4组靶点取交集获取共同靶点,利用Cytoscape软件绘制“葛根芩连汤-有效成分-共有靶点”网络图;结合STRING数据库绘制PPI网络图,再导入Cytoscape软件进行拓扑分析及可视化。运用Metascape数据库对共有靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encylopedia of genes and genomes,KEGG)通路富集分析。结果筛选并得到葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征、2型糖尿病的共同作用靶点33个。GO富集分析结果显示涉及生物过程20个,主要包括蛋白质磷酸化、炎症反应、细胞凋亡、细胞迁移等。KEGG通路信号分析以P<0.01为显著性水平,发现最小计数为3且富集因子>1.5的通路有15条,包括癌症通路、脂质和动脉粥样硬化通路、晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)等通路。结论葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征和2型糖尿病涉及33个共同靶点、20个生物过程及15种信号通路,且在临床应用中均有较好的疗效,可为进一步的实验验证及临床应用提供参考。展开更多
基金Supported by The Natural Science Foundation of Guangdong,No.S2012040006557
文摘AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.
文摘目的本文通过探究葛根芩连汤“一方治三病”的作用机制,“三病”即溃疡性结肠炎、肠易激综合征和2型糖尿病,从实际范例中寻找中医药异病同治理论的应用证据。方法采用网络药理学方法,通过中药系统药理学数据库(Traditional Chinese medicine systems pharmacology database,TCMSP)获取葛根芩连汤的主要活性成分及作用靶点,利用Gene cards、TTD、OMIM数据库获取溃疡性结肠炎、肠易激综合征和2型糖尿病3种疾病的相关靶点。将以上获得的4组靶点取交集获取共同靶点,利用Cytoscape软件绘制“葛根芩连汤-有效成分-共有靶点”网络图;结合STRING数据库绘制PPI网络图,再导入Cytoscape软件进行拓扑分析及可视化。运用Metascape数据库对共有靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encylopedia of genes and genomes,KEGG)通路富集分析。结果筛选并得到葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征、2型糖尿病的共同作用靶点33个。GO富集分析结果显示涉及生物过程20个,主要包括蛋白质磷酸化、炎症反应、细胞凋亡、细胞迁移等。KEGG通路信号分析以P<0.01为显著性水平,发现最小计数为3且富集因子>1.5的通路有15条,包括癌症通路、脂质和动脉粥样硬化通路、晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)等通路。结论葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征和2型糖尿病涉及33个共同靶点、20个生物过程及15种信号通路,且在临床应用中均有较好的疗效,可为进一步的实验验证及临床应用提供参考。
