中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (3): 580-586.doi: 10.4103/1673-5374.293153

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

三维适形调强放疗修复骨包虫病致坐骨神经损伤效果

  

  • 出版日期:2021-03-15 发布日期:2020-12-17
  • 基金资助:
    中国博士后科学基金(2019M652397)

Effect of intensity-modulated radiation therapy on sciatic nerve injury caused by echinococcosis

Wan-Long Xu1, *, Dilimulati·Aikeremu2, Jun-Gang Sun2, Yan-Jun Zhang2, Jiang-Bo Xu2, Wen-Zheng Zhou2, Xi-Bin Zhao2, Hao Wang2, Hong Yuan2   

  1. 1 Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong Province, China; 2 Department of Orthopedics, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China
  • Online:2021-03-15 Published:2020-12-17
  • Contact: Wan-Long Xu, MD, PhD, xuwanlong20082008@163.com.
  • Supported by:
    This work was supported by the China Postdoctoral Science Foundation, No. 2019M652397 (to WLX). 

摘要:

普通放射治疗对股骨棘球蚴病有很好的杀灭效果,同时也因"旁观者效应"造成病灶周围的坐骨神经受到不可逆的放射损伤。三维适形调强放疗(Intensity Modulated Radiation Therapy,IMRT)在病灶精确剂量分布方面表现出极大的优势。但IMRT是否可以在良好杀灭股骨棘球蚴病灶的基础上,完美地保护好周围的坐骨神经尚不知晓,为此,研究对比分析了三维适形调强放疗、普通放疗这两种放疗方式对周围神经安全性的差异。(1)实验以纯种双侧股骨包虫病子午沙鼠为研究对象,分别采用IMRT对子午沙鼠左侧股骨包虫病灶给予放射治疗,采用普通放疗对同一只鼠右侧股骨包虫病灶给予普通放射治疗,放疗总剂量均为40 Gy;(2)为了解三维适形调强放疗、普通放疗这两种放疗方式是否均可以对股骨棘球蚴病灶有很好的杀灭作用,实验采用锥虫蓝染色检测放疗后骨细粒棘球蚴病理学改变及原头节死亡情况、采用酶化学染色法检测放疗后原头节酸性磷酸酶的活性,照射1周后,经IMRT放射治疗的子午沙鼠双侧股骨的骨包虫原头节均整体结构消失,子午沙鼠双侧股骨的骨包虫原头节死亡率无显著差异,双侧股骨的骨包虫原头节的酸性磷酸酶活性无显著差异;(3)为了解三维适形调强放疗、普通放疗这两种放疗方式对骨包虫病灶周围坐骨神经造成的损伤,实验采用透射电镜观察放疗后坐骨神经的超微结构、TUNEL免疫组织化学染色检测、Western blot法检测放疗后坐骨神经组织中Bcl-2和Bax的表达发现,接受IMRT放疗的骨棘球蚴鼠的左侧坐骨神经大部分神经元以可逆性损伤为主,未出现明显凋亡,而且与普通放疗比较,IMRT放疗引起的坐骨神经凋亡细胞数和凋亡促进蛋白Bax的表达明显降低,凋亡抑制蛋白Bcl-2表达明显升高;(4)上述结果说明,IMRT放疗对于骨棘球蚴病治疗效果与普通放疗相同,有减轻放疗所导致的病灶周围坐骨神经组织神经元凋亡的作用。

https://orcid.org/0000-0002-5269-8987 (Wan-Long Xu) 

关键词: 细胞凋亡, 因子, 模型, 神经元, 周围神经, 可塑性, 蛋白质, 恢复, 再生, 修复

Abstract: Conventional radiotherapy has a good killing effect on femoral echinococcosis. However, the sciatic nerve around the lesion is irreversibly damaged owing to bystander effects. Although intensity-modulated radiation therapy shows great advantages for precise dose distribution into lesions, it is unknown whether intensity-modulated radiation therapy can perfectly protect the surrounding sciatic nerve on the basis of good killing of femoral echinococcosis foci. Therefore, this study comparatively analyzed differences between intensity-modulated radiation therapy and conventional radiotherapy on the basis of safety to peripheral nerves. Pure-breed Meriones meridiani with bilateral femoral echinococcosis were selected as the research object. Intensity-modulated radiation therapy was used to treat left femoral echinococcosis of Meriones meridianus, while conventional radiotherapy was used to treat right femoral echinococcosis of the same Meriones meridianus. The total radiation dose was 40 Gy. To understand whether intensity-modulated radiation therapy and conventional radiotherapy can kill femoral echinococcosis, trypan blue staining was used to detect pathological changes of bone Echinococcus granulosus and protoscolex death after radiotherapy. Additionally, enzyme histochemical staining was utilized to measure acid phosphatase activity in the protoscolex after radiotherapy. One week after radiotherapy, the overall structure of echinococcosis in bilateral femurs of Meriones meridiani treated by intensity-modulated radiation therapy disappeared. There was no significant difference in the mortality rate of protoscoleces of Echinococcus granulosus between the bilateral femurs of Meriones meridiani. Moreover, there was no significant difference in acid phosphatase activity in the protoscolex of Echinococcus granulosus between bilateral femurs. To understand the injury of sciatic nerve surrounding the foci of femoral echinococcosis caused by intensity-modulated radiation therapy and conventional radiotherapy, the ultrastructure of sciatic nerves after radiotherapy was observed by transmission electron microscopy. Additionally, apoptosis of neurons was examined using a terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and expression of Bcl-2 and Bax in sciatic nerve tissue was detected by immunohistochemical staining and western blot assay. Our results showed that most neurons in the left sciatic nerve of Meriones meridiani with echinococcosis treated by intensity-modulated radiation therapy had reversible injury, and there was no obvious apoptosis. Compared with conventional radiotherapy, the number of apoptotic cells and Bax expression in sciatic nerve treated by intensity-modulated radiation therapy were significantly decreased, while Bcl-2 expression was significantly increased. Our findings suggest that intensity-modulated radiation therapy has the same therapeutic effect on echinococcosis as conventional radiotherapy, and can reduce apoptosis of the sciatic nerve around foci caused by radiotherapy. Experiments were approved by the Animal Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region, China (Approval No. 20130301A41) on March 1, 2013. 

Key words: apoptosis, factor, model, neuron, peripheral nerve, plasticity, protein, recovery, regeneration, repair