He Xiaopo, Liu Yiran, Li Kai, Yang Aijun, Wang Rui, Liu Shaohua
School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Oral and Maxillofacial Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2645-2650. doi: 10.3892/etm.2017.4306. Epub 2017 Apr 5.
Treatment of infantile hemangiomas (IH) with propranolol was first reported in 2008. Regressions of lymphatic malformations combined with pulmonary hypertension was first reported in 2012 after three children received treatment with oral sildenafil, which serves as an antagonist of phosphodiesterase isoform-5 (PDE-5). A marked expression of endothelial cells in the cytoplasm of IH tissues was obtained in our previous study. Therefore, the present study hypothesized that the antagonist of PDE-5, sildenafil, may lead to the regression of hemangiomas. To assess this hypothesis, the proliferation and apoptosis of specimen-derived hemangioma endothelial cells (HemECs) was determined by an MTT assay and flow cytometry, respectively, following treatment with sildenafil. The potential mechanisms underlying the mRNA and protein expression levels of inhibitor of differentiation 1 (Id-1) were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that 5 µM sildenafil suppressed the proliferation of HemECs and significantly enhanced the rate of apoptosis after 24 h. Additionally, the mRNA and protein expression levels of Id-1 were downregulated following treatment with sildenafil. Therefore, the present study concluded that PDE-5 may be a potential therapeutic target for hemangiomas and Id-1 may serve a vital role in the associated signaling transduction pathways.
2008年首次报道了用普萘洛尔治疗婴儿血管瘤(IH)。2012年,在3名儿童接受口服西地那非治疗后,首次报道了淋巴管畸形合并肺动脉高压的消退情况,西地那非是磷酸二酯酶同工酶-5(PDE-5)的拮抗剂。在我们之前的研究中,在IH组织的细胞质中获得了内皮细胞的显著表达。因此,本研究假设PDE-5的拮抗剂西地那非可能导致血管瘤消退。为了评估这一假设,在用西地那非处理后,分别通过MTT法和流式细胞术测定标本来源的血管瘤内皮细胞(HemECs)的增殖和凋亡。通过逆转录定量聚合酶链反应和蛋白质印迹法确定分化抑制因子1(Id-1)的mRNA和蛋白质表达水平的潜在机制。结果表明,5μM西地那非抑制了HemECs的增殖,并在24小时后显著提高了凋亡率。此外,在用西地那非处理后,Id-1的mRNA和蛋白质表达水平下调。因此,本研究得出结论,PDE-5可能是血管瘤的潜在治疗靶点,Id-1可能在相关信号转导途径中起重要作用。