OK-432和西地那非治疗儿童淋巴管畸形机制的探讨

Lymphatic malformation (lymphangioma, LM) is a common form of congenital vascular malformation in children. Generally, LM is regarded as benign anomalies, but they can suddenly expand in size, involve vital structures, impair function, or causing long-term sequelae. Over the past several decades, various therapeutic management options have been explored for LM. But, current therapeutic modalities are limited. Resently, Swetman reported that sildenafil may help treat lymphatic malformations. But the sildenafil's mechanism of action in lymphatic malformations remains unclear. So, in this research we aimed to develop the in vivo and in vitro LM models and to examine the expression changes of Vascular endothelial growth factor C(VEGF-C) and Vascular endothelial growth factor receptor 3(VEGFR-3)in the LM tissues of this two models during treated with sildenafil and OK-432 respectively.And to study the inhibition of VEGF-C expression, using short hairpin RNA (shRNA) in vivo and in vitro. The long term goal of this pilot project is to achieve a greater understanding of the pathogenesis of LM and the mechanism of sildenafil treatment. To provide a experimental tool and proof for clinic therapies.

淋巴管畸形(淋巴管瘤）为儿童常见疾病，虽然被认为是良性病变，但其易并发感染且难以控制；而生长部位特殊的则常导致毁容、畸形、功能障碍甚至危及生命。目前有关其的治疗方法很多，但效果却不理想。近来，新英格兰杂志报道了口服西地那非能有效治疗儿童淋巴管畸形，但其治疗机制尚不清楚。本研究拟通过建立能客观、真实地反映人淋巴管畸形临床发展过程的细胞培养模型及裸鼠移植模型，对比观测在分别经西地那非和OK-432治疗的各时期中，两种模型上淋巴管畸形的生长及变化情况。观测两模型淋巴管畸形中血管内皮生长因子C（VEGF-C）和血管内皮生长因子受体3（VEGFR-3）表达的变化及淋巴管内皮细胞数量和形态的变化，并采用VEGF-C 短发夹RNA(shRNA) 慢病毒质粒转染人淋巴管畸形细胞株抑制VEGF-C的表达，以探讨淋巴管畸形的发病机制及西地那非治疗该病的可能机制。为临床应用西地那非治疗淋巴管畸形提供理论依据。

淋巴管畸形(淋巴管瘤）为儿童常见疾病，虽然被认为是良性病变，但其易并发感染且难以控制；而生长部位特殊的则常导致毁容、畸形、功能障碍甚至危及生命。目前有关其的治疗方法很多，但效果却不理想。近来，新英格兰杂志报道了口服西地那非能有效治疗儿童淋巴管畸形，但其治疗机制尚不清楚。本研究通过建立能客观、真实地反映人淋巴管畸形临床发展过程的组织培养模型、裸鼠移植模型及SD大鼠淋巴管畸形模型，对比观测在分别经西地那非和OK-432治疗的各时期中，三种模型上淋巴管畸形的生长及变化情况。观测了三种模型淋巴管畸形中血管内皮生长因子C（VEGF-C）和血管内皮生长因子受体3（VEGFR-3）表达的变化及淋巴管内皮细胞数量和形态的变化，探讨淋巴管畸形的发病机制。并证实了西地那非干预三种模型的确能抑制淋巴管畸形内皮细胞的生长，并探讨了其可能的机制。为临床应用西地那非治疗淋巴管畸形提供了理论依据。

内容获取失败，请点击重试