放射性口腔黏膜炎患者外周血循环血管内皮细胞的动态水平

Analysis of Circulating Endothelial Cells in Patients with Radiation-induced Oral Mucositis

【目的】检测头颈癌放疗患者不同时期循环内皮细胞(CEC)及循环内皮祖细胞(CEP)的动态变化,探讨血管内皮细胞损伤在放射性口腔黏膜炎(RTOM)病理生理过程中起的作用。【方法】头颈部癌放疗确诊患者24例,征得患者知情同意后,流式细胞法检测放疗前(0 Gy)、放疗早期(20 Gy)、放疗中期(40 Gy)和放疗末期(60 Gy)外周血中CEC和CEP的水平,同时观察患者RTOM病损情况,获得口腔黏膜炎指数(OMI)和疼痛评分(NRS)。【结果】头颈癌放疗患者CEC的数量在放疗后各期与放疗前的差异有统计学意义(P<0.05);CEC与OMI(r=0.719,P<0.05)和NRS呈统计学正相关关系(r=0.628,P<0.05);其中RTOM严重(OMI>2)患者组的CEC在放疗后各期均较RTOM轻微患者(OMI≤2)增加,差异有统计学意义(P<0.05);患者CEP的数量在放疗早期较放疗前减少,至末期又逐渐增长(P<0.05);其中在放疗末期RTOM严重患者组与轻微RTOM患者组CEP的差异有统计学意义(P<0.05)。【结论】黏膜下血管内皮损伤和修复贯穿整个放疗过程与RTOM的发展密切相关,可能是RTOM重要的始发和促进因素。CEC可能是判断RTOM严重程度的早期非侵袭性指标。CEP则为防治RTOM的新靶标。

[Objective] To investigate the dynamic changes of circulating endothelial cells （CEC） and circulating endothelial progenitor cells （CEP） at different time points of radiotherapy （RT） in head and neck cancer patients,and explore the possible relationship between endothelial damage and pathogenesis of radiation-induced oral mucositis （RTOM）.[Methods] After provided informed consent,24 head and neck cancer patients who received radiotherapy were enrolled for evaluation of CEC and CEP.The peripheral venous blood samples were drawn at four time point,pre-radiation（0 Gy）,the early stage of RT（20 Gy）,the middle stage of RT （40 Gy）,and the end stage of RT （60 Gy）.The number of CEC and CEP were detected by flow cytometry.The severe of RTOM was graded at the same time-points by oral mucositis index （OMI） evaluation and Numerical Rating Scale （NRS）.[Results] Patients undergoing RT had significantly increased number of endothelial damage marker CEC in 20 Gy,40 Gy and 60 Gy in comparison to 0 Gy （P ＜ 0.05）.There was significant positive correlation （r =0.719,r =0.628,P ＜ 0.05） between the CEC and RTOM grade （OMI and NRS）;The CEC of patients with more several RTOM toxicity （OMI ＞ 2） had increased than patients with mild toxicity （OMI ＜ 2） in 20 Gy,40 Gy and 60 Gy （P＜ 0.05）.Significant reduced in the number of CEP were observed in 20 Gy in comparison to 0 Gy,and gradually increased in 60 Gy （P ＜ 0.05）;and the increase in this subpopulation was most marked in patients with Grade 3 peak toxicity or greater at the end of RT.[Conclusions] The activities of injury and repairment to endothelial cells happened throughout the whole process of RT and closely related to RTOM.It suggested that the damage of endothelial cells may be the initiating and promoting factors of RTOM and CEC may be a non-invasive and early marker of assessing the severity of RTOM.On the other hand,our finding suggests that CPC could be a novel target for radioprotective strategies.