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低能量体外冲击波治疗联合低张牵引可更好地重塑退变椎间盘再生修复的微环境。

Low energy extracorporeal shock wave therapy combined with low tension traction can better reshape the microenvironment in degenerated intervertebral disc regeneration and repair.

机构信息

Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital of SooChow University, 708 Renmin Rd, Suzhou, Jiangsu 215007, People's Republic of China; Department of Orthopedics, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, People's Republic of China.

Department of Geriatrics, Xinghu Hospital, SuZhou industrial park, Suzhou, Jiangsu, People's Republic of China; Department of Endocrinology, The First Affiliated Hospital of SooChow University, Suzhou, Jiangsu, People's Republic of China.

出版信息

Spine J. 2021 Jan;21(1):160-177. doi: 10.1016/j.spinee.2020.08.004. Epub 2020 Aug 13.

Abstract

BACKGROUND

Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited.

PURPOSE

To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action.

STUDY DESIGN

Animal study of a rat model of degenerated discs.

METHODS

A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured.

RESULTS

After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers.

CONCLUSIONS

Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.

摘要

背景

低张力牵引比高张力牵引更能有效恢复退变椎间盘的高度和再水化,并在一定程度上恢复骨性终板。这可能会更好地重塑椎间盘再生和修复的微环境。然而,终板硬化、骨赘形成,甚至塌陷导致营养通道部分或几乎完全闭塞的组合的修复受到极大限制。

目的

评估低强度体外冲击波疗法(ESWT)联合低张力牵引对中重度退变椎间盘的再生和修复的有效性;探讨其可能的作用机制。

研究设计

大鼠退变椎间盘的动物研究。

方法

35 只 6 月龄雄性 Sprague-Dawley 大鼠随机分为 5 组(n=7,每组)。在 A 组(模型组)中,使用定制的外部设备固定尾椎以固定四个尾椎(Co7-Co10),而 Co8-Co9 经历 4 周的压缩以诱导中度椎间盘退变。在 B 组(实验对照组)中,与 A 组一样,成功诱导椎间盘退变后,去除固定装置 8 周进行自我恢复。其余三组为干预组(C-E 组):C 组(com-4w/tra-4w)和 D 组(com-4w/ESWT)在成功产生椎间盘退变后,如 A 组所述,进行低张力牵引(原位牵引)或低能量 ESWT 治疗 4 周(ESWT 参数:强度:0.15 Mpa;频率:1 Hz;冲击:每次 1,000 次;每周 1 次,共 4 次);E 组(com-4w/tra-4w/ESWT):如 A 组所述产生椎间盘退变,进行低张力牵引联合低能量 ESWT(ESWT 参数如 D 组)。实验结束后,采集尾椎,测量椎间盘高度、T2 信号强度、椎间盘形态、总糖胺聚糖(GAG)含量、基因表达、Co8-Co9 骨性终板结构和椎间盘弹性模量。

结果

连续低张力牵引、低能量 ESWT 干预或联合干预后,退变椎间盘有效恢复高度并重新水化。然而,与其他干预组相比,D 组在恢复椎间盘高度方面的反应较弱,而 E 组在椎间盘再水化方面表现更好。C 组至 E 组的不同干预措施均显示组织再生。实验对照组(B 组)未见明显组织再生。三组干预组(C-E 组)的组织学评分均低于 A 组或 B 组(p<.0001),C 组和 E 组的评分明显低于 D 组(p<.05),但 C 组与 E 组之间无差异(p>.05)。与干预组(C-E 组)相比,B 组髓核(NP)的总 GAG 含量无明显增加(p>.05)。A 组和 B 组之间总 GAG 含量也无差异(p>.05)。在三个干预组中,E 组 NP 的 GAG 含量恢复最大。纤维环(AF)中胶原 I 和 II 以及聚集蛋白的表达上调(p<.05),而基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-13(MMP-13)和 ADAMTS-4 的表达下调(p<.05)。E 组的基因表达调节程度最大。NP 中 GAG 表达的调节趋势与 AF 的基本一致,其中 E 组最大。在干预组(C-E 组)中,与 A 组相比,骨性终板的孔结构发生了明显变化。C 组至 E 组终板中的孔数明显高于 A 组(p<.0001),其中 C 组与 D 组之间(p=.9724)和 C 组与 E 组之间(p=.0116)存在显著差异。A 组与 B 组之间无差异(p=.5261)。此外,孔径也增大,趋势与孔密度基本一致。三组干预组之间无差异(p=.7213)。值得注意的是,与 A 组和 B 组相比,D 组和 E 组三个干预组的外周孔密度和大小均显著恢复。AF 和 NP 中的胶原纤维的弹性模量和直径随干预类型而变化。低张力牵引联合 ESWT 对胶原纤维的直径和模量产生了最大的影响。

结论

低能量 ESWT 联合低张力牵引为中重度退行性椎间盘的再生和修复提供了更稳定的椎间环境。低能量 ESWT 通过减少 MMP-3、MMP-13 和 ADAMTS-4 促进椎间盘基质的再生,从而抑制胶原降解。尽管轴向牵引促进了 IVD 高度和再水化的恢复,但与低能量 ESWT 结合时,骨性终板的微纳米结构发生了积极的重建,AF 环的张力和 NP 的核压下降,重塑了椎间盘再生和修复所需的生物力学微环境。

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