感觉神经逆分泌作用下神经肽SP对婴幼儿血管瘤病程发展的影响

Infantile hemangioma is the most common benign tumor of infants and young children with the cause is unknown, and complex factors involved in course of development. Mechanism with the progress of spontaneous regression is not clear. Part IH on the distribution of segments characteristics was consider to related with innervation. Early studies have demonstrated that the number of nerve fibers in the proliferation period IH was increased obviously than involuted period IH. Neural factors may be involved in the course of IH development process. Sensory nerve reverse secretion is a hotspot of recent studies. Our preliminary experiments had demonstrated that SP substances could mediated HemECs cell proliferation activity. On this basis, we propose hypothesis that, SP, mediated by dysfunction of nerve function, may play a key role in regulation IH disease course. To verify the hypothesis, immunohistochemistry and electron microscopy experimental techniques will be used to determine the distribution of nerve in IH, and through the co-culture system of HemECs and mast cell to observe the effects of substance P in cell function changes within the system, and finally verified the nerve malfunction in regulation the course of IH by animal experiments.

婴幼儿血管瘤是婴幼儿最常见良性肿瘤，病因不明，参与病程发展因素复杂，自发消退机制不清。IH在分布上具有一定神经节段性特点，普萘洛尔治疗和其神经肽阻断药理可能有相关性，早期研究发现增殖期IH内感觉神经纤维数量明显多于消退期，感觉神经异常可能参与了IH病程发展。感觉神经逆向分泌作用近期研究广泛，SP是其分泌的主要神经肽，广泛参与肿瘤等病程发展过程，和肥大细胞关系密切。我们预实验已经证实，神经因素在IH病程发展中有重要作用，发现SP能够促进HemECs的增殖。据此我们提出假设，感觉神经异常分泌下，SP介导的细胞功能异常在IH病程发展中起到了关键调控作用。为验证假设，拟通过免疫组化及电镜等实验技术确定神经纤维在IH中的分布异常，及与普萘洛尔治疗的相关性，并通过HemECs和肥大细胞的共培养体系观察SP对体系内细胞功能改变的影响，通过富感觉神经异常IH动物模型，验证感觉神经异常对IH病程发展的影响

婴幼儿血管瘤是一种先天性血管肿瘤，是儿童最常见的软组织肿瘤。一般在出生后一周到数周时间内开始发病，随后病程发展过程大致可以分为增殖期、 消退期和消退完成期。在本研究中，并未发现不同分期的婴幼儿血管瘤标本中有明显神经分布。此外，我们发现婴幼儿血管瘤组织中的PGP9.5的表达较正常皮肤组织高，但在不同分期的标本中的表达无特异性。用脐静脉内皮细胞（HUVEC）进行相关生物学实验发现，较SP抑制剂，SP激动剂可以促进HUVEC细胞增殖，但对其迁移和侵袭能力没有显著影响。另外，SP无促进肥大细胞释放组胺的作用，且肥大细胞无促进HUVEC细胞增殖的能力。