中文摘要
研究显示,血管生成与纤维化疾病关系密切,而血小板活化既是克罗恩病(CD)临床活动度的重要指标,亦是介导血管生成的重要途径。我们前期研究发现:三棱丸对CD患者的肠纤维化(IF)疗效明确,并在实验室研究中初步得到证实,明确其作用机制对临床治疗具有重要意义。在此基础上我们提出假说“肠微血管内皮细胞(IMECs)的血管生成由血小板活化通过PI3K/AKT/mTOR关键信号通路介导,并调控HIF-lα,继而形成IF;三棱丸通过这一通路调控血管生成,发挥抗IF作用。”为进一步阐明假说,采用免疫组化、免疫荧光、Western blotting、RT-PCR和siRNA干扰等技术手段,系统研究三棱丸对大鼠肠纤维化模型血小板活化、血管生成、纤维化的作用,及对血小板活化介导的IMECs血管生成的干预,围绕调控血管生成的PI3K/AKT/mTOR信号通路,阐明其治疗IF的分子作用机制,为临床治疗提供依据。
英文摘要
Studies have revealed that angiogenesis is tightly linked to fibrotic disease, and the platelet activation is not only an important indicator of the clinical activity of Crohn's disease (CD), but also a significant way to mediate angiogenesis. In our previous study, Sparganium Pill has a therapeutic effect to CD patients with intestinal fibrosis (IF), which had been verified elementarily in the laboratory research. It is of great significance to clarify the mechanism for clinic treatment of IF. Based on the finds above, we propose the hypothesis that angiogenesis of intestinal microvascular Endothelial Cells (IMECs) mediated by platelet activation regulates HIF-lα through the key signaling pathway of PI3K/AKT/mTOR and resluts the final formation of IF, and Sparganium pill plays the role of anti IF by regulating the angiogenesis through the pathway mentioned above. In order to clarify the hypothesis further, we plan to study systematically the effect on the platelet activation, angiogenesis and fibrosis of intestinal fibrosis model, the intervention in angiogenesis of IMECs mediated by platelet activation in vitro by Sparganium Pill with the technologies of immunohistochemistry, immunofluorescence, Western blotting, RT-PCR, siRNA and so on. Around the PI3K/AKT/mTOR signaling pathway of angiogenesis regulation, the results from this study will reveal the molecular mechanisms of Sparganium Pill treating IF and provide the scientific evidences for clinical application.
