中文摘要
婴幼儿血管瘤(IH)是婴幼儿最常见的良性肿瘤,血管瘤内皮细胞(HemECs)作为IH的最主要细胞成分,在IH的增殖中起重要作用。基于磷酸二酯酶5(PDE5)抑制剂西地那非能够有效治疗血管瘤这一临床发现,结合前期研究,我们认为:西地那非通过作用于HemECs而抑制IH的增殖。本项目从2个方面探讨西地那非的作用及机制:① 西地那非对HemECs的增殖及凋亡的影响;② 通过病毒转染沉默PDE5,并检测细胞增殖、凋亡及下游cGMP表达水平的变化,进一步明确西地那非影响IH增殖的分子机制。该项目将在现有学说基础上进一步分析IH的发病机制,研究西地那非对IH增殖的影响,为该病及血管相关性疾病的药物治疗提供新思路。
英文摘要
Infantile hemangioma (IH) is the most common benign tumor in infancy. Hemangioma endothelial cells (HemECs), which is the main component of IH, play an important role in the proliferation of IH. Accoroding to the clinical finding that sildenafil, a phos-phodiesterase 5 (PDE5) inhibitor, could effectively treat IH, and combining with our previous studies, we proposed that sildenafil could inhibit the proliferation of IH by acting on the HemECs. This project will test this hypothesis and explore its mechanism following the approaches as below. Firstly, we will test the effect of sildenafil on the proliferation and apoptosis of HemECs. Secondly, we will silence the PDE5 via virus transfection of siRNA, and then test the variation of the proliferation and apoptosis of the HemECs to confirm the mechanism of sildenafil effecting the proliferation of IH. Our research will make a further exploration on the mechanism of the infantile hemangioma, and reveal the effect of sidenafil on the proliferation of IH, in order to pave a novel way for the drug therapy of IH and related vascular diseases.
结题摘要
婴幼儿血管瘤(IH)是婴幼儿最常见的良性肿瘤,血管瘤内皮细胞(HemECs)作为IH的最主要胞成分,在IH的增殖中发挥了重要作用。基于磷酸二酯酶5(PDE5)抑制剂西地那非能够有效治疗血管瘤这一临床发现,我们认为:西地那非通过抑制HemECs的增殖并促进其凋亡从而治疗血管瘤。本项目从2个方面探讨了西地那非的作用及机制:①西地那非对HemECs的增殖及凋亡的影响;②通过沉默PDE5,并检测细胞增殖、凋亡及下游cGMP表达水平的变化,进一步探讨西地那非影响IH增殖的分子机制。研究结果发现,西地那非抑制了HemECs的增殖并促进了其凋亡,而且这种作用是通过PDE5-cGMP实现的。该项目明确了西地那非对血管瘤内皮细胞的影响作用,并初步探讨了其作用机制,为该病及血管相关性疾病的药物治疗提供了新思路。
