HSP27在腹泻型肠易激综合征中的作用及机制研究

Irritable bowel syndrome (IBS) is a common disease of digestive system with unknown mechanism and rare effective treatment. Diarrhea-predominant irritable bowel syndrome (IBS-D) is most harmful type of IBS that many factors involved in its pathogenesis. Recent studies have found that immune response mediated by TLR4/MyD88/NF-κB signaling pathway can generate low-grade inflammation which play a role in pathogenesis of IBS-D, but the mechanism is unknown. Some results and our group's preliminary study indicate heat shock protein 27 (HSP27) high expression in IBS-D,other report finds HSP27 inhibit TLR4/MyD88/NF-κB signaling pathway in amoeba infection. So we speculate HSP27 play a role in IBS-D by changing TLR4/MyD88/NF-κB signaling pathway. Therefore, our study will observe changes of HSP27 and TLR4/MyD88/NF-κB signaling pathway and its relevance in IBS-D rats animal models, then study the effect and target of HSP27 to TLR4/MyD88/NF-κB signaling pathway by cytology test.Further,we will confirm related hypothesis and mechanisms in IBS-D rats animal models and patients with IBS-D. This study aims to find effect and mechanism of HSP27 to IBS-D and provide a theoretical basis for IBS-D in the pathogenesis, diagnosis and treatment.

肠易激综合征（IBS）是一种消化系常见病，机制不明、缺乏有效治疗手段。其中，腹泻型IBS（IBS-D）危害最大，多因素参与发病。近期研究发现TLR4/MyD88/NF-κB信号通路介导免疫反应产生低度炎症在其发病中发挥作用，但机制不明。已有发现及课题组前期初步研究提示热休克蛋白27（HSP27）在IBS-D中高表达，另有报道阿米巴感染时HSP27抑制TLR4/MyD88/NF-κB信号通路，故推测HSP27可能通过改变TLR4/MyD88/NF-κB信号通路在IBS-D中发挥作用。故本课题拟在IBS-D大鼠中研究HSP27与TLR4/MyD88/NF-κB信号通路的变化及其相关性，通过细胞学实验探讨HSP27对该通路的作用及靶点，并在动物模型及IBS-D患者中验证相关假说及机制。本研究旨在明确HSP27对IBS-D的作用及其机制，为阐明IBS-D发病机制和寻找有效诊疗手段提供理论依据。

肠易激综合征（IBS）是一种消化系常见病，机制不明、缺乏有效治疗手段。其中，腹泻型IBS（IBS-D）危害最大，多因素参与发病。近期研究发现低度炎症在IBS-D发病中发挥作用，但机制不明。本课题通过体内外实验发现HSP27总蛋白及其磷酸化形式在IBS-D肠粘膜中含量增高，HSP27主要通过其磷酸化抑制IκB-a的磷酸化，进而抑制NF-κB的激活及肠粘膜炎症反应、抑制细胞凋亡及促进细胞增殖等。小肠细菌过度生长可诱导IBS-D患者HSP27的表达及肠道炎症反应，调整小肠细菌过度生长可降低HSP27的表达、缓解IBS-D患者炎症反应及症状。本课题完善了IBS-D的发病机制，提出调整小肠细菌过度生长及靶向HSP27-IκB-a-NF-κB通路可能作为IBS-D治疗的重要方案，对基础科研及临床都有一定的指导作用。.本研究结果发表SCI论文2篇，中文核心期刊论文8篇，在第五届北京消化疾病学术周末会议暨京津冀消化-肝病-消化内镜协同发展促进会进行口头发言交流。课题实施过程中，培养科学型硕士研究生2名，科学型博士研究生2名。