【作者】 张平；

【导师】 许成蓉；

【作者基本信息】 华中科技大学 ， 皮肤病与性病学， 2006， 硕士

【摘要】 血管瘤是一种血管内皮组织来源的良性肿瘤,是新生儿肿瘤中最为常见的一种。血管瘤有其特征性的临床表现,早期阶段表现为瘤体迅速增生,然后大部分血管瘤可发生自发性的消退。尽管在大多数情况下,血管瘤可自发消退而无并发症的出现。但是在少数病例中,由于血管瘤在一些重要器官或部位发生增殖,会对生命构成威胁。发生在头面部的血管瘤,因严重影响面部美观,甚至产生畸形,而对病患及家属带来身心上的严重伤害。对于血管瘤,目前的治疗还不是很充分。因此深入认识血管瘤增生期和消退期的发生机制对血管内皮细胞的生物行为和血管生成的研究具有深刻的意义。目前,对于血管瘤的治疗包括药物治疗和手术切除。皮质类固醇激素、干扰素、长春新碱对血管瘤的治疗有一定疗效,但药物治疗的副作用和并发症局限了药物治疗的应用。因此亟待研制特异性强的新型药物,这就需要对血管瘤发生发展的细胞和分子生物学机制进行更深入的研究。已有证据显示IGF-II可能在血管瘤的发生发展中扮演重要的角色。我们前期的研究中发现IGF-II在血管瘤的增生期中高表达,而在其消退期恢复低水平。由于IGF-II作为丝裂原可促细胞增殖,抑制细胞凋亡,因此我们推测IGF-II作为促生长因子与血管瘤的增生密切相关。在血管瘤增生期中,IGF-II有可能与其它因子相互联系,使其自分泌或旁分泌的水平增高,通过与血管瘤内皮细胞上的IGF-IR结合,刺激血管瘤的增殖。自1986年IGF-IR被Ullrich等首次克隆以来,对它的研究已受到越来越多的关注。早先,它被认为是一种与IR相关的受体,它们在结构上具有70%同源性,在功能上被认为是一种多余的受体,仅在IR缺陷的细胞中,发挥替代作用。随着研究的深入,IGF-IR被确定为一种独立的受体,尽管与IR的功能有部分的重叠,但却发挥着不同的功能,特别在细胞凋亡、肿瘤分化,细胞寿命等诸多方面发挥重要的作用。本实验中,我们将首次研究IGF-IR在血管瘤发生发展中的表达变化,以探讨其作为血管瘤治疗靶点的可能性。采用免疫组化SP法和半定量RT-PCR法检测不同分期(增殖期和消退期)血管瘤中IGF-IR的表达水平,并与血管畸形及正常皮肤标本进行比较。SP法和半定量RT-PCR法结果均显示增殖期血管瘤内皮细胞IGF-IR表达水平增高,与血管畸形及正常皮肤组织间差异显著(P<0.01);而消退期的IGF-IR表达水平与血管畸形及正常皮肤组织相比,差异无显著性(P>0.05)。实验结果提示IGF-IR与血管瘤的发生发展有密切关系,IGF-IR可作为血管瘤增殖期特定标志,为皮肤血管瘤的鉴别诊断与早期治疗提供了新的思路。更多还原

【Abstract】 Hemangiomas are benign tumors of the vascular endothelium and are the most common tumors of infancy. These tumors are characterized by an initial phase of rapid proliferation, which is followed, in most cases, by spontaneous involution. Although most lesions resolve without complication, there are some cases in which hemangiomas can be life threatening when occurring near a vital structure. Hemangiomas, particularly facial lesions, can be disfiguring and also often carry a significant psychosocial component for the patient and family. Treatment for these aggressive tumors represents an unmet clinical need. In addition, this characteristic progression of hemangiomas through distinct phases provides a unique opportunity for studying endothelial cell biology and angiogenesis.Therapy includes corticosteroid, interferon, vincristine, and, sometimes, surgical resection. However, these pharmacological treatments are not without side effects and complications .Targeted therapy will require a better understanding of the cellular and molecular basis underlying the pathogenesis of this tumor.There was also evidence that IGF-II may have roles in angiogenesis and hemangiomas. IGF-II is a reasonable putative regulator of hemangioma proliferation, because it is a known mitogen and suppresses apoptosis. The function of this protein has been characterized, as has its primary functional receptor, IGF-IR. Although its expression profile was not as dramatic, IGF-I cannot be ruled out as a potential stimulator of hemangioma growth, and it is possible in fact, that IGF-I and IGF-II have cooperative effects because they share IGF-IR as a major receptor.The existence of the type I insulin-like growth factor receptor (IGF-IR) had been surmised for a number of years, before it was cloned in 1986 by Ullrich et al. At that time, the IGF-IR was considered a poor relative of the insulin receptor (IR), with which it has a 70% homology, a sort of redundant receptor that the cells used when the IR was defective. The past years have established the IGF-IR as an independent receptor, with overlapping, but different, functions from the IR and playing important roles in apoptosis, cancer, differentiation and even longevity. Many commentary focus on the role of the IGF-IR in cancer, with special emphasis on its use as a possible target for therapeutic purposes.In the present study, we study the relationship between IGF-IR and the progress of hemangioma. The expression of IGF-IR in the difference stages (proliferative stage and involuting stage) of hemangiomas was measured using SP immunohistochemical method and RT-PCR, comparing with vascular malformation and normal skin tissues at same time. The results of both SP immunohistochemical method and RT-PCR showed that the expression of IGF-IR in the proliferative stage of hemangioma was much higher than that in vascular malformation and normal skin tissues. The expression of IGF-IR in the insolving stage of hemangioma was decreased to a similar level to vascular malformation and normal skin tissues. There is significantly positive correlation between the expression of IGF-IR and proliferative degree of hemangioma, IGF-IR can provide information for the differential diagnosis of hemangioma which may provide a new train of though for finding the target to diagnose and treat hemangioma.更多还原