Xiong Ying, Berrueta Lisbeth, Urso Katia, Olenich Sara, Muskaj Igla, Badger Gary J, Aliprantis Antonios, Lafyatis Robert, Langevin Helene M
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.
Front Immunol. 2017 Feb 16;8:124. doi: 10.3389/fimmu.2017.00124. eCollection 2017.
Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model.
The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2 BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching for 10 min daily versus no stretching.
Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2.
Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.
尽管物理治疗有助于系统性硬化症（SSc）患者保持活动能力，但伸展运动尚未被系统地用作预防或逆转疾病进程的治疗方法。我们之前在啮齿动物模型中表明，伸展运动可促进结缔组织炎症的消退，并减少损伤后新胶原蛋白的形成。在此，我们使用小鼠硬皮病移植物抗宿主病（sclGvHD）模型，测试了伸展运动会影响硬皮病发展这一假设。
该模型包括将B10.D2小鼠的脾细胞（移植物）过继转移（同种异体）到Rag2 BALB/c宿主（sclGvHD）中，导致皮肤炎症，随后在4周内出现纤维化。将sclGvHD小鼠和对照组随机分为每日伸展10分钟组和不伸展组。
每周对背部皮肤厚度和皮下组织活动度进行超声测量（被动躯干运动期间的相对组织位移）成功捕捉到了sclGvHD模型的不同阶段。与第3周不伸展相比，伸展可降低皮肤厚度并增加皮下组织活动度。伸展还在第4周降低了皮肤中CCL2和ADAM8的表达，这两个基因在小鼠sclGvHD和人类SSc的炎症亚组中均上调。然而，没有证据表明伸展在第2周减轻了炎症。
在sclGvHD小鼠模型中，在没有任何其他治疗的情况下，每日伸展10分钟可改善皮肤厚度和活动度。这些临床前结果表明，有必要对伸展运动作为一种治疗方式在SSc患者中进行系统研究。
