激光针促VEGF-C及VEGF-D在治疗乳腺癌相关淋巴水肿机制中的作用

The overall increase in incidence of breast cancer and significant morbidity related to its treatment has raised renewed attention to the management of arm lymphedema in recent years. Breast-cancer-related lymphedema (BCRL), the onset of lymphedema secondary to breast cancer treatment is a chronic disease which often leads to a chronic condition of functional disability, disfigurement and inflammatory attacks. Even conservative approaches to treat breast cancer, like sentinel lymph node sampling and selective axillary clearance, have failed to erradicate lymphatic complications. Currently there is no definitive treatment for it. There are some therapeutic interventions targeted to decrease the limb swelling and the associated problems, including acupuncture. But due to the possibility of infection, very few researches have been reported on using acupuncture to treat BCRL either domestic or abroad. Laser acupuncture (LA) is a treatment in which low-energy laser beams are used to electronic current at acupuncture points. Low-level laser therapy (LLLT) has been used in the treatment of BCRL recently. It is described mechanisms of volume reduction include promotion of lymphangiogenesis and lymphaticmotility stimulation, improve overall lymphatic flow and reduce interstitial fibrosis which accompanies lymph stasis. The most advantage of using laser acupuncture over using needles is its non-invasiveness, which offers the possibility for the therapists to conduct treatment by using local acupoints on the edema arm. Vascular endothelial growth factor-C (VEGF-C) and D （VEGF-D）are the primary regulators of lymphangiogenesis in developmental and pathological conditions. VEGF-C and VEGF-D combined with their receptor-3 (VEGFR-3) can induce the growth of new lymphatic vessels, improve lymphatic function and reverse the abnormalities in tissue architecture resulting from chronic lymphatic insufficiency, suggesting that some forms of lymphedema might be treated by similar approaches. While vascular endothelial growth factor-A (VEGF-A) combined with its receptor-2 (VEGFR-2) is closely related with microvascular regeneration. The aim of this research is to study the mechanism of the laser acupuncture treatment on BCRL. We hypothesize that laser acupuncture worked through promoting serum VEGF-A,VEGF-C or VEGF-D that resulted in the improvement of both microvascular cycle regenerataion and lymphatic function,which will lead to the alleviation of BCRL.

乳腺癌相关淋巴水肿（BCRL）是乳腺癌患者术后继发的慢性疾病，严重影响其生活质量。目前西医无根治方法。激光针治疗BCRL既能产生针刺疗效，又能避免传统针刺在患肢取穴造成侵入性感染的安全隐患。低强度激光可在一定程度上增加淋巴和免疫系统活力、激发细胞组织内生长因子、改善淋巴回流，但其作用机理尚未明确。血管内皮生长因子VEGF-A 与微血管的再生密切相关，VEGF-C及VEGF-D（又称淋巴管内皮生长因子）对淋巴管的生成至关重要。本研究在明确激光针治疗BCRL临床疗效的基础上，拟证实其作用机制是通过激光针刺激局部穴位，诱导血清VEGF-A生成增加并与其受体VEGFR-2结合， 促进微血管的再生而加强微循环；促进VEGF-C和VEGF-D生成并与其受体VEGFR-3结合，使淋巴管内皮细胞发生增殖与迁移。其结果是局部淋巴管新生、侧支循环建立、淋巴回流和滁留改善，为解决BCRL提供新的治疗途径。

背景：乳腺癌相关淋巴水肿（BCRL）是乳腺癌幸存者在手术或放疗后继发的常见症状。激光针穴位照射是一种用低能量激光代替传统针刺对穴位进行刺激的疗法。 我们设计了一个临床试验证明使用激光针穴位照射治疗BCRL的安全性，评估其临床疗效。在确认临床疗效的基础上，观察血清血管内皮生长因子 (VEGF-A、C、D)及血管生成素-1(ANG-1)在体内的变化，探讨作用机制。.方法: 开展随机对照的临床试验。随机分为治疗组和对照组，两组在维持原有常规治疗的基础上，治疗组采用632.8nm氦氖激光照射穴位（极泉，肩髃，尺泽，曲泽，合谷，液门，气海，水分，阴陵泉，足三里），每次治疗25分钟，每周2次，连续治疗6周，共治疗12次；对照组为等待组，入组10周内不接受激光针治疗，仅维持原有常规治疗，入组10周后接受与治疗组相同的治疗。分别在入组时0周，入组后3周、6周和治疗结束后4周测量双上肢的臂围，入组时0周，入组后6周和治疗结束后4周3次采集外周血。检测血清VEGF-A、VEGF-C、VEGF-D及ANG-1的表达。.结果:.1.两组患者一般资料具有可比性。治疗是安全可行的。治疗组治疗3周,治疗6周后与治疗前比较，患侧臂围均显著减小（症状减轻），差异有统计学意义(P<0.001)；等待组入组3周、入组10周时与入组前比较，患侧臂围差异无统计学意义(P>0.05)，等待组入组6周后与入组前比较，患侧臂围增大（症状加重），差异有统计学意义(P=0.029)； 治疗组治疗3周、治疗6周及治疗结束后4周随访时患侧臂围改善率均明显高于对照组（均P<0.001）。.2.治疗组与等待组患者的血清VEGF-A、VEGF-C、VEGF-D及ANG-1浓度在入组前、入组6周、入组10周无统计学差异（P>0.05）；治疗时间、组别与治疗时间的交互作用对4个指标的影响均无统计学意义（P>0.05）。